Radiolabelled vitamers of vitamin b3, and their derivatives and analogues as radiotracers and radiotherapeutic agents

Abstract

Provided are vitamers of vitamin B3 and their derivatives and analogues as radiopharmaceutical compounds, more specifically either as radiotracers for nuclear imaging techniques or as radiotherapeutic agents. Imaging methods, including diagnostic imaging methods, which utilize the radiotracers are also provided.

Description

[0001]RADIOLABELLED VITAMERS OF VITAMIN B3, AND THEIR DERIV- ATIVES AND ANALOGUES AS RADIOTRACERS AND RADIOTHERAPEU- TIC AGENTS FIELD OF THE INVENTION The present invention relates to the field ofnuclear medicine, in particular to vitamers of vitaminB3 and their derivatives and analogues as radiopharma-ceutical compounds, and their use as radiotracers fornuclear imaging techniques, including position emissiontomography (PET) imaging and single-photon emission com-puted tomography (SPECT), and as radiotherapeuticagents. BACKGROUND OF THE INVENTION Vitamin B3 is an essential nutrition for hu- mans, and it is vital for the normal function of the nervous system and body energy production. In light of emerging other roles of vitamin B3 both in human health and diseases, there is a need for novel tools for non-invasive imaging of tissues and organs that express mol-ecules interacting with vitamin B3, and to advance the understanding of the role of vitamin B3 in clinical treatment. This translates into a need for novel diag- nostic and therapeutic agent for the management of dis- eases in which vitamin B3 plays a role. WO 2009129573 discloses some nicotinamide de-rivatives for imaging or treating melanoma. Use of these compounds for imaging or treating other cancers in not suggested. SUMMARY Provided herein is a radiopharmaceutical com-pound or a pharmaceutically acceptable salt thereof for use in imaging or treating cancer, the radiopharmaceu- tical compound having the general formula (I): (I) wherein X is nitrogen or carbon; R1is selected from the group consisting ofhydroxyl, amino, amide, dexamethasone, alkyl ester, phe-nyl ester, and polyethylene glycol amide; R2 is hydrogen or riboside;R3 is a radionuclide, hydrogen, or alkyl;R4is a radionuclide, hydrogen, or alkyl; with the proviso that at least one of R3and R4is a radionuclide, andwith the proviso that if X is nitrogen and R1is amide, said cancer is not melanoma. Also provided is a radiopharmaceutical com-pound having the same general Formula (I) set forthabove, wherein X is nitrogen or carbon; R1 is selected from the group consisting of hydroxyl, amine, dexamethasone, alkyl ester, phenyl es- ter, and polyethylene glycol amide; R2 is hydrogen or riboside;R3is a radionuclide, hydrogen, or alkyl; R4is a radionuclide, hydrogen, or alkyl; with the proviso that at least one of R3and R4is a radionuclide, with the proviso that when X is carbon, R1is not hydroxyl, and with the proviso that the alkyl ester of R1is not ethyl ester, when R3is radionuclide and R4is hy- droxyl, or pharmaceutically acceptable salt thereof. Also provided is a radiopharmaceutical compo-sition comprising a radiopharmaceutical compound pro-vided herein or a pharmaceutically acceptable saltthereof in a pharmaceutically acceptable carrier solu-tion. Also provided is a method for imaging a sub- ject, the method comprising: administering a radiopharmaceutical compoundor a radiopharmaceutical composition provided herein tothe subject; allowing the radiopharmaceutical to accumulate in tissues and organs of the subject; and providing an image obtained by a nuclear imag- ing technique, preferably a PET or SPECT image, showing whether said accumulation has occurred or not. Also provided is a precursor compound for a radiopharmaceutical compound provided herein, the pre- cursor compound having a general formula (II): wherein XPis nitrogen or carbon; R1Pis selected from the group consisting of OH (hydroxyl), NH2 (amino, amide), dexamethasone, alkyl ester, phenyl ester, and polyethylene glycol amide; R2Pis selected from the group consisting of hydrogen and riboside; and R3Pis trimethylammonium trifluoroacetate, tri-methylammonium acetate, and trimethylammonium trifluo-romethanesulfonate, when R4Pis selected from the group consisting of methyl, ethyl, and hydroxyl; or R3Pis selected from the group consisting of methyl, ethyl, and hydroxyl, when R4Pis selected fromthe group consisting of trimethylammonium trifluoroace-tate, trimethylammonium acetate, and trimethylammonium trifluoromethanesulfonate; or R3Pand R4Pare both selected, independentlyfrom each other, from the group consisting of trime-thylammonium trifluoroacetate, trimethylammonium ace-tate, and trimethylammonium trifluoromethanesulfonate.Also provided is use of the precursor compoundsfor the preparation of corresponding radiopharmaceuti- cal compounds provided herein, as well as corresponding preparation methods. Also provided is use of a compound having the general Formula (III): wherein: XRis nitrogen or carbon; R1Ris selected from the group consisting of hydroxyl, amino, amide, dexamethasone, alkyl ester, phe- nyl ester, and polyethylene glycol amide; R2Ris hydrogen or riboside; R3R is hydrogen, alkyl, or non-radioactive flu-orine or iodine;R4R is hydrogen, alkyl, or non-radioactive flu-orine or iodine; with the proviso that least one of R3Rand R4Ris non-radioactive fluorine or iodine, as a reference compound for a corresponding radiopharmaceutical compound provided herein. Some embodiments of the invention are set forth in the dependent claims. Further embodiments and aspects become apparent from the detailed description, the fig- ures and the examples. BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings, which are included to provide a further understanding of the invention and constitute a part of this specification, illustrate em- bodiments of the invention and together with the de- scription help to explain the principles of the inven- tion. In the drawings: Figure 1A is a schematic representation of thesynthesis of [18F]niacin (i.e. [18F]fluoronicotinicacid). Figure 1B shows a quality control (QC) of[18F]niacin with high performance liquid chromatography(HPLC) analysis at end of synthesis under radioactivitydetection. Figure 1C shows a quality control (QC) of[18F]niacin with HPLC analysis at 4 h after end of syn-thesis under radioactivity detection. Figure 1D shows HPLC analysis of reference 6-fluoronicotinic acid (6-fluoroniacin) under UV detec-tion at wavelength of 220 nm. Figure 2 illustrate PET / CT imaging of [18F]ni-acin uptake in mice with or without glioblastoma. PanelsA and B show that glioblastoma was clearly visualizedwith [18F]niacin PET, whereas Panel C shows that theuptake was diminished with monocarboxylate transporter1 (MCT1) blocking. Panel D shows PET / CT imaging ofhealthy mice as controls. Panel E shows time-activitycurves of tumor uptake in the presence or absence of blockers. Panel F demonstrates that fasting for 4 hours did not have influence on tumor uptake of [18F]niacin which is a favorable property for clinical use. Figure 3 shows the comparison PET imaging with[18F]niacin (A), [11C]methionine (B) and [18F]FDG (C). Itis clearly shown that the PET imaging performance of [18F]niacin is superior to the current clinical radio- pharmaceuticals [11C]methionine and [18F]FDG. Figure 4 shows the biodistribution of [18F]ni-acin in mice bearing glioblastoma, with MCT1 blockingand GPR109A inhibition. This also demonstrates that[18F]niacin PET is a powerful tool to profile the tissue distribution in the whole body. Figure 5 clearly shows the focal and intenseuptake of glioblastoma in the brain tissue samples. Figure 6 shows the time-activity curves (TACs)of lung, heart, blood and liver. This gives the im- portant information about the biokinetics of [18F]niacin in these organs. Figure 7 is high performance liquid chromato-graphs of reference standard (A) and plasma samples (B) from mice. This is a concrete evidence that [18F]niacin is stable in vivo, which is a key parameter in new radiopharmaceutical development. Figure 8 demonstrates PET imaging of human tri-ple-negative breast cancer brain metastasis in a mouse model. Figure 9 demonstrates PET imaging of B16-lucmelanoma metastasis in liver in a mouse model with nor- mal immunity. DETAILED DESCRIPTION The present invention relates to radiolabelled vitamers of vitamin B3and their derivatives and ana-logues as radiopharmaceutical compounds. As used herein, the term “radiolabelled” refers to a compound that has a radioactive nuclide in its chemical structure. As used herein, the term “vitamer” refers to any and all of two or more related forms of a particular vitamin, each performing the functions of said vitamin and relieving the deficiency of said vitamin. As used herein, the term “vitamers of vitaminB3” include, but are not limited to, three vitamers,namely niacin, niacinamide and niacinamide riboside. Niacin is also known as nicotinic acid, and pyridine-3- carboxylic acid; whereas niacinamide is also known as nicotinamide and pyridine-3-carboxamide. As used herein, the term “radiopharmaceuticalcompound” refers to a radioactive compound intended foradministration to a subject for use in in vivo imaging,such as diagnostic imaging, in therapy, or in any invitro applications.As used herein, the term “subject” refers to amammal, preferably to a human. In some embodiments, saidsubject may suffer from a disease such as cancer, espe-cially glioblastoma, with or without diagnosis, be sus-pected to suffer from said disease, be at risk of said disease, or may have already been treated for said dis- ease. In some other embodiments, especially in those relating to research purposes, said subject may be ap- parently healthy. The radiopharmaceuticals disclosed herein in- clude vitamers of vitamin B3 and their derivatives andanalogues having a general formula (I): wherein: Xis nitrogen or carbon;R1 is selected from the group consisting ofhydroxyl, amino, amide, dexamethasone, alkyl ester, phe- nyl ester, and polyethylene glycol amide; R2 is hydrogen or riboside;R3 is a radionuclide, hydrogen, or alkyl;R4 is a radionuclide, hydrogen, alkyl;with the proviso that least one of R3and R4is a radionuclide; or a pharmaceutically acceptable salt thereof. As used herein, the term “alkyl ester” in- cludes, but is not limited to methyl ester and ethyl ester. As used herein, the term “alkyl” includes, butis not limited to, methyl, ethyl, propyl and butyl. Inan embodiment, the alkyl is methyl. As used herein, the term “pharmaceutically ac-ceptable salt” includes, but is not limited to, saltssuch as acetate salts, trifluoroacetate salts, trifluo- romethanesulfonate salts of the radiopharmaceutical compounds of general Formula (I). As used herein, the terms “radionuclide” and radioisotope” are used interchangeably, and refer to a form of a chemical element that shows radioactivity. Preferred radionuclides for use in the present radio- pharmaceuticals include, but are not limited to, fluo-rine-18 (18F), iodine-123 (123I), iodine-124 (124I), io-dine-125 (125I), iodine-131 (131I), and astatine-211(211At). In some embodiments, radiopharmaceutical com- pounds of Formula (I) include those wherein X and R2areas defined above (i.e. X is hydrogen or carbon, and R2is hydrogen or riboside), R1 is ethyl ester or methylester, R3 is a radionuclide when R4 is hydrogen, or R3is hydrogen when R4is a radionuclide. In some embodiments, radiopharmaceutical com-pounds of Formula (I) include those wherein X, R1 and R2are as defined above (i.e. X is hydrogen or carbon, R1is selected from the group consisting of hydroxyl, amino, amide, dexamethasone, alkyl ester, phenyl ester, and polyethylene glycol amide, and R2is hydrogen or riboside), R3is a radionuclide when R4is hydrogen, or R3is hydrogen when R4is a radionuclide. In some embodiments, radiopharmaceutical com- pounds of Formula (I) include those wherein X is hydro- gen or carbon, R1is selected from the group consisting of hydroxyl, amino, dexamethasone, alkyl ester, phenyl ester, and polyethylene glycol amide, and R2is hydrogen or riboside), R3is a radionuclide when R4is hydrogen, or R3is hydrogen when R4is a radionuclide, optionally with the proviso that when X is carbon, R1is not hy- droxyl, and / or with the proviso that the alkyl ester of R1is not ethyl ester, when R3is radionuclide and R4is hydroxyl. In some embodiments, radiopharmaceutical com- pounds of Formula (I) include those wherein X is hydro- gen or carbon, R1 is selected from the group consisting of hydroxyl, dexamethasone, alkyl ester, phenyl ester, and polyethylene glycol amide, and R2is hydrogen or riboside), R3 is a radionuclide when R4 is hydrogen, or R3is hydrogen when R4is a radionuclide, optionally with the proviso that when X is carbon, R1is not hy- droxyl, and / or with the proviso that the alkyl ester of R1is not ethyl ester, when R3is radionuclide and R4is hydroxyl. In some embodiments, radiopharmaceutical com-pounds of Formula (I) include those wherein X, R1 and R2are as defined above, and both R3and R4are radionu-clides. The radionuclides of R3 and R4 may be the sameor different radionuclides. In some embodiments, radiopharmaceutical com-pounds of Formula (I) include those wherein X, R1 and R2are as defined above, and R3is a radionuclide when R4is methyl, or R3 is methyl when R4 is a radionuclide. In some embodiments, the radiopharmaceuticalcompound is a vitamer of vitamin B3radiolabelled withfluorine-18 (18F) such that either R3 is fluorine-18 andR4 is hydrogen, R3 is hydrogen and R4 is fluorine-18, orboth R3and R4are fluorine-18. Further embodiments of18F-labelled radiophar- maceutical compounds include those wherein X is N, R1iseither OH (hydroxyl) or NH2 (amino, amide), and R2 is,independently from R1, either hydrogen or riboside. Em-bodiments wherein R3 is fluorine-18 and R4 is hydrogeninclude, but are not limited to, the following radio- pharmaceutical compounds: [18F]niacin, also called [18F]fluoronicotinicacid or 5-[18F]fluoronicotinic acid, i.e. a compoundhaving the formula: ; [18F]niacinamide, also called [18F]fluoronico-tinamide or 5-[18F]fluoronicotinamide, i.e. a compoundhaving the formula: ; and 6-[18F]fluoronicotinamide riboside, i.e. a com- pound having the formula: ; whereas embodiments wherein R3 is hydrogen and R4 is fluorine-18 include: 5-[18F]fluoronicotinic acid, 5-[18F]fluoronicotinamide, and 5-[18F]fluoronicotinamide riboside. A non-limiting example of a radiopharmaceuti-cal compound of Formula (I) in which X is carbon, is 3-[18F]fluoro-4-methylbenzoic acid, i.e. a compound havingthe formula: . Corresponding compounds contain-ing different radionuclides are also included.A non-limiting example of a radiopharmaceuti- cal compound of Formula (I) in which R1is dexamethasone, is[18F]fluorodexamethasone, i.e. q compound having the formula: cluded. A non-limiting example of a radiopharmaceuti- cal compound of Formula (I) in which R1is ethyl ester is ethyl 6-[18F]fluoro-5-methylnicotinate, i.e. a com- pound having the formula: . Corresponding compounds con-taining different radionuclides are also included. A non-limiting example of a radiopharmaceuti- cal compound of Formula (I) in which R1is methyl ester is methyl 6-[18F]fluoro-5-methylnicotinate, i.e. a com- pound having the formula: . Corresponding compounds con-taining different radionuclides are also included. A non-limiting example of a radiopharmaceuti- cal compound of Formula (I) in which R1is polyethyleneglycol amide is 6-([18F]fluoro)-N-(14-phenyl-3,6,9,12-tetraoxatet-radecyl)nicotinamide, i.e. a compound hav- ing the formula: . Corresponding compounds containing different radionu- clides are also included. 18F-labelled radiopharmaceutical compounds areparticularly suitable for positron emission tomography(PET). Accordingly, in some embodiments, said compoundsare provided as radiotracers for non-invasive PET imag-ing, including total-body imaging as well as imaging oflocalised regions of the body or single organs of in-terest, such as a brain, a liver, a lung, a breast, acolon, a stomach, a bladder, a prostate, a testis, oran ovary. Notably, the present radiotracers are to be used as such, i.e. without conjugation to another mo-lecular entity, such as a protein, for said PET imaging.PET imaging is a diagnostic technique utilizedin various medical and research environments to produceimages that reveal functional features of a subject’sbody. This is achieved through visualizing the distri- bution of a radiopharmaceutical compound within a spe- cific area of the body. For the execution of PET imaging,the radiopharmaceutical compound is typically injectedinto the patient, allowing it to circulate via thebloodstream and to accumulate into the target organ. APET scanner is then used to monitor the concentrationof the radiopharmaceutical compound within the organ invivo as the PET isotope emits positrons and decays. PETtechnology is capable of creating both dynamic andstatic imaging, which can be rendered in two or threedimensions. PET imaging is often combined with ComputedTomography (CT) to produce composite images that merge anatomical structure with functional data. Addition- ally, PET imaging is often used in combination with Magnetic Resonance Imaging (MRI). Single-photon emission computed tomography (SPECT) imaging is a diagnostic nuclear imaging tech-nique similar to PET. Those skilled in the art under-stand the similarities and differences, and can readilyadopt the present radiopharmaceuticals depending on whether PET or SPECT is to be employed. As the SPECT imaging is based on gamma ray-emitting radioactive trac- ers,211At-labelled radiopharmaceutical compounds areparticularly suitable for SPECT. For the execution of SPECT imaging, the radiopharmaceutical compound is typ- ically injected into the patient, allowing it to circu- late via the bloodstream and to accumulate into the target organ. A SPECT scanner is then used to monitor the concentration of the radiopharmaceutical compoundwithin the organ in vivo as the radionuclide emits gammarays and decays. A 3D image of the radioactivity dis-tribution can be computed by acquiring multiple 2D im-ages at various angles, the 2D images generated by typ- ically two detectors present in an SPECT scanner. The present radiopharmaceutical compounds tar- get molecular entities that are capable of interactionwith vitamers of vitamin B3, and their derivatives andanalogues. Such molecular entities include receptors,including G-protein coupled receptor GPR109A, also knownas hydroxycarboxylic acid receptor 2 (HCAR2), an im- portant metabolite-sensing receptor that is widely dis-tributed in human tissues. Another example of such re-ceptors is GPR109B, which also has important roles invitamin B3 metabolism in disease and health. Accordingly, the present radiopharmaceutical compounds provided as radiotracers, preferably as18F- labeled or211At-labeled radiotracers, may be used for imaging tissues, organs and other regions of the body that contain healthy or diseased cells that express saidreceptors. GPR109A, a G-protein coupled receptor forniacin, has been implicated in various aspects of dis- ease and health. Initially, GPR109A expression was thought to be limited to adipocytes and immune cells, aligning with niacin's anti-lipolytic and anti-athero- genic effects. However, its expression in other cell types has been associated with anti-inflammatory func- tions, and its role in cancer as a potential tumor sup- pressor has been highlighted. In the context of diabe- tes, GPR109A's relevance is underscored by the need for new therapies targeting inflammation to prevent and treat diabetic retinopathy. Conversely, niacin's acti- vation of GPR109A in pancreatic islet beta-cells has been linked to impaired glucose-stimulated insulin se- cretion and beta-cell dysfunction, suggesting a detri-mental effect in the context of hyperglycemia. Inter-estingly, while GPR109A's role in the oral microbiota is not directly discussed, the microbiota's influence on systemic diseases, including inflammation, suggests a potential indirect connection to GPR109A's anti-in- flammatory properties. In neurodegenerative diseases, GPR109A's brain-specific counterpart, HCAR2, has been shown to be neuroprotective in Alzheimer's disease mod- els, indicating a protective role in neuroinflammation and cognitive decline. The broader implications of mi- crobiota in disease pathogenesis, including autoimmune diseases, further support the importance of understand- ing GPR109A's role in immune modulation. The Inventors have obtained evidence that[18F]niacin, its derivatives and analogues are trans- ported by monocarboxylate transporters (MCTs). In other words, MCTs are also the drug targets of [18F]niacin and the related compounds, and hence included in the molec- ular entities capable of interaction with the presentradiopharmaceuticals. MCTs are implicated in variousdiseases due to their role in transporting key metabolic substrates such as lactate, pyruvate, and ketone bodies across cell membranes. In metabolic disorders, MCTs fa- cilitate the uptake of circulating succinate by brown adipose tissue, which can counteract obesity and sys- temic inflammation. MCTs are also overexpressed in sev- eral cancers, where they contribute to the altered me- tabolism and acidic resistance of cancer cells, making them targets for therapeutic intervention. For instance, in prostate cancer, MCT2 and MCT4 are associated with early diagnosis and poor prognosis, respectively, and MCT1 and MCT4 are considered potential therapeutic tar- gets. Additionally, mutations in MCT8 are linked to Al- lan-Herndon-Dudley syndrome, a condition characterized by intellectual disability. Interestingly, while MCT1 is primarily responsible for succinate import in brown adipocytes, other MCT family members can compensate in its absence, indicating redundancy and complexity in MCT function. Moreover, MCTs are not only involved in lac- tate transport but also participate in pH regulation and fluid transport in various tissues. This multifunction- ality underscores the potential impact of MCTs on dis- ease pathophysiology beyond metabolic disorders and can- cer, including neurodegenerative diseases and brain en-ergy metabolism. Accordingly, the present radiotracersmay find broad use in disease management and research.According to experimental results by the In-ventors, but without being limited to any theory or mode of action, MCT1, MCT2 and MCT4 are critical transporters and targets for the present radiopharmaceuticals. There- fore, the present radiopharmaceuticals can be used for imaging or treating any cancers which express MCT1, MCT2or MCT4. This includes not only primary tumors but alsotheir metastasis. Examples of cancers that can be imagedor treated by the present radiopharmaceuticals include, but are not limited to, glioma, glioblastoma, brain me- tastasis, breast cancer, colon cancer, lung cancer, prostate cancer, ovarian cancer, cell carcinoma, gas- trointestinal stromal tumors, head and neck cancer, mel- anoma, liver cancer, bladder cancer, and testicular can- cer. In accordance with the above, provided hereinis use of the present radiopharmaceutical compounds forimaging cancer, including but not limited to the cancerslisted above and / or cancers that express MCT1, MCT2 orMCT4. In an embodiment, use of radiopharmaceutical compounds of general Formula (I), wherein X is nitrogenand R1 is amide for imaging melanoma is excluded. How-ever, use of these compounds for imaging other cancers is not excluded. In an embodiment, the use for imaging cancerconcerns a radiopharmaceutical compound of general For-mula (I), wherein X is nitrogen or carbon; R1 is selectedfrom the group consisting of hydroxyl, dexamethasone, alkyl ester, phenyl ester, and polyethylene glycol am-ide; R2 is selected from the group consisting of hydro-gen, and riboside; R3 is a radionuclide, hydrogen, oralkyl; R4 is a radionuclide, hydrogen, or alkyl; withthe proviso that at least one of R3and R4is a radio-nuclide, or pharmaceutically acceptable salt thereof.Some further embodiments concern use of any one of the radiopharmaceutical compounds specifically dis- closed in this specification, as well as pharmaceuti-cally acceptable salts thereof, for imaging cancer. Thisapplies especially to the 18F-labeled or 211At-labeledradiopharmaceuticals. An aspect of the invention may be provided asa method of in vivo locating, imaging or visualizingcells that are positive for molecular entities capable of interaction with vitamers of vitamin B3, or deriva- tives and analogues thereof in a subject, the method comprising administering to the subject a radiopharma- ceutical compound according to the present invention. To be more specific, the radiopharmaceutical is admin- istering to the subject such that it enters the blood- stream of the subject. After allowing the radiopharma-ceutical to accumulate in the tissue, organ or otherregion of interest, the accumulation, i.e. uptake, (ifany) is evaluated by PET or SPECT imaging as known to those skilled in the art. Detected accumulation or up- take of the radiopharmaceutical compound is indicative of the presence of cells that express a molecular en- tity, such as a receptor capable of interaction with a vitamer of vitamin B3, or a derivative or an analogue thereof. The present radiopharmaceutical compounds pro- vided as radiotracers may thus be employed for imaging any tissue, organ or other region of interest for the presence or absence of cells that express cells thatexpress a molecular entity capable of interaction witha vitamer of vitamin B3, or a derivative or an analoguethereof. Organs and tissues that may be imaged (i.e.visualized) using the present radiopharmaceutical com- pounds include, without limitation, brain, heart, pan-creas, retina, liver, breast, colon, lung, prostate,testis, ovary, head and neck, bladder adipose tissue, and cancer tissue. In accordance with the above, provided is a method for imaging a subject, the method comprising: administering a radiopharmaceutical compoundaccording to the invention, or a pharmaceutical compo- sition comprising said radiopharmaceutical compound to the subject; allowing the radiopharmaceutical compound to accumulate in tissues and organs of the subject; and detecting by a nuclear imaging technique, suchas PET or SPECT imaging, whether said accumulation hasoccurred or not. The last step of the method may alsobe expressed as obtaining a PET or SPECT image showingwhether said accumulation has occurred or not. Accumu-lation of the radiopharmaceutical is indicative of the presence of cells that express a molecular entity, suchas a receptor, capable of interaction with a vitamer ofvitamin B3, or with its derivative or analogue. The method may thus be denoted as a method for imaging a subject for one or more tissues or organs positive fora molecular entity, such as a receptor, capable of in-teraction with a vitamer of vitamin B3, or a derivative or an analogue thereof. As used herein, the term “allowing the radio- pharmaceutical compound to accumulate” does not mean that the radiopharmaceutical compound necessarily accu- mulates in the tissue or organ to be imaged, but that sufficient time has elapsed from the administration en- abling the radiopharmaceutical compound to accumulate in said tissue or organ if it comprises cells that ex-press a molecular entity capable of interaction with avitamer of vitamin B3, or a derivative or an analogue thereof. Administration of the radiopharmaceutical such that it enters the bloodstream of the subject contrib- utes to said accumulation. Herein, the terms “accumula- tion” and “uptake” may be used interchangeably. In an embodiment, an organ to be visualized by nuclear imaging is the brain. Accordingly, provided is a method of imaging brain of a subject, the method com- prising: administering a radiopharmaceutical compound according to the invention, or a pharmaceutical compo- sition comprising said radiopharmaceutical compound to the subject; allowing the radiopharmaceutical to accumulate in the brain of the subject; and detecting by a nuclear imaging technique, suchas by PET or SPECT imaging, whether said accumulationhas occurred in the brain or not, or to put it differ-ently: obtaining a PET or SPECT image of the brain show-ing whether said accumulation has occurred or not. Ac-cumulation of the radiopharmaceutical is indicative of the presence of cells that express a molecular entity,such as a receptor, capable of interaction with vitamersof vitamin B3, or a derivative or an analogue thereof. It has now been surprisingly realized that the above-described method may also be used for detecting or diagnosing glioma including glioblastoma, a high- grade brain tumor originating from astrocytes. There- fore, provided is a method of detecting or diagnosing glioma in a subject, the method comprising: administering a radiopharmaceutical compound according to the invention, or a pharmaceutical compo- sition comprising said radiopharmaceutical compound to the subject; allowing the radiopharmaceutical to accumulate in the brain of the subject; obtaining an image, such as a PET or SPECTimage, of the brain by a nuclear imaging technique; anddetecting or diagnosing glioma on the basis ofsaid image. In some embodiments, said glioma is glio-blastoma. In accordance with the above, the present method is in some embodiments directed to diagnosing ofglioblastoma or another glioma, i.e. determining whetheror not a subject suspected of having glioblastoma oranother glioma indeed appears to have glioblastoma oranother glioma as determined by uptake of the presentradiopharmaceutical compound in the subject’s brain. It has now been also surprisingly realized that the above-described method may also be used for detect-ing or diagnosing brain metastases, such as brain me-tastases originating from breast cancer. Therefore, theabove disclosure concerning imaging, detecting or diag- nosing glioma or glioblastoma applies also to imaging, detecting or diagnosing brain metastases as appropriate. It has also been surprisingly realized that the above-described method may not only be used for detect-ing or diagnosing brain cancers or brain metastases butalso other cancers and metastases such as those thatexpress MCT1, MCT2 or MCT4. Therefore, the above dis-closure concerning imaging, detecting or diagnosing gli- oma or glioblastoma applies also to imaging, detecting or diagnosing other cancers and metastases as appropri- ate. Imaging, detecting or diagnosing cancers isalso meant to include instances where the presence ofcancer, such as glioblastoma or another glioma, is not finally determined but that further diagnostic testing is warranted. In such embodiments, the method is not by itself determinative of the presence or absence of can-cer, such as glioblastoma or another glioma, in thesubject but can indicate that further diagnostic testing is needed or would be beneficial, or the method can be used to confirm the diagnosis obtained by other means. Therefore, the present method may be combined with oneor more other diagnostic methods for the final determi-nation of the presence or absence of cancer, such asglioblastoma or another glioma, in the subject. Suchother diagnostic methods are well known to a personskilled in the art, including for example computed to- mography (CT) and magnetic resonance imaging (MRI). In some implementations, the above-described methods may further include therapeutic intervention. Once a subject is determined have cancer, such as gli-oblastoma or other glioma, he / she may be subjected totreatment that is predicted to be effective. Such meth- ods may be formulated in different ways. For example, in some embodiments, the present invention provides amethod for treating cancer (e.g. glioblastoma or anotherglioma), in a subject in need thereof, said method com-prising: administering a radiopharmaceutical compound according to the invention, or a pharmaceutical compo- sition comprising said radiopharmaceutical compound to the subject; allowing the radiopharmaceutical to accumulatein an organ (e.g. the brain) of the subject;obtaining an image of the organ (e.g. thebrain) by a nuclear imaging technique such as PET orSPECT; and when the image shows accumulation of the radi-opharmaceutical in the organ (e.g. the brain), deter-mining that said organ is afflicted by cancer, and treating said subject for said cancer (e.g. glioblastomaor another glioma) with surgery, radiation therapy,chemotherapy, immunotherapy or targeted therapy such as therapy with small molecule inhibitors, or any combina- tion thereof. Alternatively or in addition, any of the above-described methods may include monitoring response to treatment, monitoring relapse of the disease in ques-tion, or monitoring recurrence of the disease. In suchmethods, monitoring is carried out by repeating the PET imaging at different time points to detect any change in the accumulation of the radiopharmaceutical as com- pared to one or more earlier PET or SPECT images obtained from the same subject. The present radiopharmaceutical compounds may also be used as tools for various research purposes. Positron emission tomography (PET) imaging and single-photon emission computed tomography (SPECT) imaging arevaluable techniques for in vivo visualization of recep-tor expression in various tissues, including the brain and heart. It allows for the non-invasive quantification of receptor binding, which is crucial for understanding the pathophysiology of diseases and for the development of targeted therapies. For instance, PET imaging has been utilized to detect the peripheral benzodiazepine receptor expression in neuroinflammatory disorders, providing insights into the neuroinflammatory response to cerebral insults. Similarly, PET imaging of low-den- sity lipoprotein receptors (LDLr) and other molecular targets has been instrumental in the early diagnosis of atherosclerotic lesions, potentially preventing prema- ture death caused by atherosclerosis. Therefore, the radiotracers described herein can be used as a non- invasive imaging tool for clinical target profiling, monitoring treatment-response, and development of new drugs. 18F-labelled radiopharmaceutical compounds of the present invention, including but not limited tothose exemplified above, are suitable not only as radi-otracers but also as radiotherapeutic agents. This ap- plies to other disclosed radiopharmaceutical compounds, too. Thus for the sake of clarity, disclosed radiother- apeutic compounds include those having general Formula (I) as defined in its broadest sense, that is wherein Xis nitrogen or carbon; R1 is selected from the groupconsisting of hydroxyl, amino, amide, dexamethasone,alkyl ester (such as methyl ester, ethyl ester), phenylester, and polyethylene glycol amide; R2 is selectedfrom the group consisting of hydrogen, and riboside; R3 is a radionuclide, hydrogen, or alkyl (such as methyl); R4is a radionuclide, hydrogen, or alkyl (such as me-thyl); with the proviso that at least one of R3 and R4is a radionuclide, the radionuclide being selected fromthe group consisting of fuorine-18 (18F), iodine radio-isotopes such as iodine-123 (123I), iodine-124 (124I),iodine-125 (125I), iodine-131 (131I), and astatine radi-oisotopes, such as astatine-211 (211At). If both R3 andR4are radionuclides, they may be either the same or different radionuclides. In an embodiment, provided is a radiopharma-ceutical compound of general Formula (I) as defined inthe previous paragraph with the exception that R1is selected from the group consisting of hydroxyl, dexame- thasone, alkyl ester (such as methyl ester, ethyl es- ter), phenyl ester, and polyethylene glycol amide, and with the proviso that when X is carbon, R1is not hy-droxyl, and with the proviso that the alkyl ester of R1is not ethyl ester, when R3is radionuclide and R4is hydroxyl. In an embodiment, provided is a radiopharma-ceutical compound of general Formula (I) for use intreating cancer, wherein the general Formula (I) is as defined in the paragraph preceding the previous para- graph, with the proviso that when X is nitrogen and R1is amide, said cancer is not melanoma. In other words, amide-substituted pyridine carboxamide radiopharmaceu-ticals of Formula (I) are excluded from being providedas radiotherapeutics for use in treating melanoma. How-ever, these compounds are provided as radiotherapeuticsfor use in treating cancers other than melanoma.Further embodiments provide any one of the ra-diopharmaceutical compounds specifically disclosed inthis specification, as well as pharmaceutically accepta-ble salts thereof, for use in treating cancer. Thisapplies especially to the radiopharmaceuticals labelledwith radioactive iodine or astatine. In some embodiments, the radiopharmaceutical compound of the invention is a vitamer of vitamin B3orits derivative or analogue, labelled with a radioisotopeof iodine, such as iodine-131 (131I), iodine-125 (125I),iodine-123 (123I), and iodine-124 (124I), a radioisotopeof astatine, such as astatine-211 (211At). The radionu- clide may be at the 6-position (R3) and / or at the 5- position (R4) of the general formula (I). Thus, in some embodiments, R3is the radionuclide, if R4is hydrogen, or vice versa. In some other embodiments, both R3and R4may be the radionuclide. In some embodiments of the radiopharmaceuticalcompound according to the general formula (I), R3 ishydrogen and R4is selected from the group consisting of iodine-131, iodine-125, iodine-124, and astatine-211. In a more specific embodiment, a radiopharmaceuticalcompound of the general formula (I) wherein X is nitro-gen, and R4is iodine-123, when R1is hydroxyl and R2ishydrogen is excluded.Further embodiments of radiopharmaceutical compounds labelled with radioactive iodine include thosewherein X is N, R1 is either OH or NH2, and R2 is,independently from R1, either hydrogen or riboside. Em- bodiments where R3is iodine and R4is hydrogen include, but are not limited to, the following radiopharmaceuti- cal compounds: 6-[131I]iodonicotinic acid, i.e. a compound having the formula: ; 6-[131I]iodonicotinamide, i.e. a compound hav- ing the formula: ; and6-[131I]iodonicotinamide riboside, i.e. a com- pound having the formula: ; whereas embodiments where R3is hydrogen and R4is a radioisotope of iodine include: 6-[123I]iodonicotinic acid, 6-[124I]iodonicotinic acid, 6-[125I]iodonicotinic acid, 6-[123I]iodonicotinamide, 6-[124I]iodonicotinamide, 6-[125I]iodonicotinamide, 6-[123I]iodonicotinamide riboside, 6-[124I]iodonicotinamide riboside, 6-[125I]iodonicotinamide riboside, 5-[123I]iodonicotinic acid, 5-[124I]iodonicotinic acid, 5-[125I]iodonicotinic acid, 5-[123I]iodonicotinamide, 5-[124I]iodonicotinamide, 5-[125I]iodonicotinamide, 5-[123I]iodonicotinamide riboside, 5-[124I]iodonicotinamide riboside, and 5-[125I]iodonicotinamide riboside. Also included are radiopharmaceutical com- pounds that correspond to the radiopharmaceutical com- pounds described above, but where the iodine is replaces with astatine such as astatine-211. Furthermore, there can be dual labelled com- pounds with two radionuclides at a time. Non-limiting examples of the present radiopharmaceutical compounds include: 5-[18F]-6-[123I]-iodofluoronicotinic acid, 5-[18F]-6-[124I]-iodofluoronicotinic acid, 5-[18F]-6-[125I]-iodofluoronicotinic acid, 5-[18F]-6-[123I]-iodonicotinamide, 5-[18F]-6-[124I]-iodonicotinamide, 5-[18F]-6-[125I]-iodofluoronicotinamide, 5-[18F]-6-[123I]-iodofluoronicotinamide riboside,5-[18F]-6-[124I]-iodofluoronicotinamide riboside, 5-[18F]-6-[125I]-iodofluoronicotinamide riboside, 5-[123I]-6-[18F]-iodofluoronicotinic acid, 5-[124I]-6-[18F]-iodofluoronicotinic acid, 5-[125I]-6-[18F]-iodofluoronicotinic acid, 5-[123I]-6-[18F]-iodofluoronicotinamide, 5-[124I]-6-[18F]-iodofluoronicotinamide, 5-[125I]-6-[18F]-iodofluoronicotinamide, 5-[123I]-6-[18F]-iodofluoronicotinamide riboside, 5-[124I]-6-[18F]-iodofluoronicotinamide riboside, and 5-[125I]-6-[18F]-iodofluoronicotinamide riboside. Radiopharmaceutical compounds labelled withradioactive iodine or astatine are particularly suitable for therapeutic purposes. Therefore, in some embodimentssaid compounds are provided as radiotherapeutic agents,especially for treating diseases that involve a molec-ular entity, such as a receptor, capable of interactionwith a vitamer of vitamin B3. In an embodiment, saiddisease is glioma, especially glioblastoma. The presentradiotherapeutic agents are preferably used as such, i.e. without conjugation to another molecular entity, such as a drug. As used herein, the terms "treating", "treat-ment", and the like, refer to a therapeutic method thatinvolves administration of a radiopharmaceutical com-pound of the invention to a subject in need thereof suchthat it enters the bloodstream of the subject, for apurpose which may include ameliorating, lessening, in- hibiting or curing of the disease in question, such as glioblastoma. An embodiment of the above aspect provides amethod for treating glioma, such as glioblastoma, in asubject in need thereof, said method comprising admin-istering a therapeutically effective amount of a radi-opharmaceutical compound of the invention to the sub-ject. As used herein, the term “therapeutically ef- fective amount” refers to an amount of a radiopharma- ceutical compound by which harmful effects of the dis-ease are, at a minimum, ameliorated.Amounts and regimens for administration of thepresent radiopharmaceutical compounds can be determined readily by those skilled in the art. Generally, dosing will vary depending on considerations such as: age, gen- der and general health of the subject to be treated; kind of concurrent treatment, if any; severity and type of the disease; causative agent of the disease and other variables to be adjusted by the individual physician. Radiotherapy with a radiopharmaceutical com- pound of the invention may be combined with one or more other therapies selected from surgery, chemotherapy, immunotherapy, targeted therapy such as therapy withsmall molecule inhibitors, and radiation therapy withone or more further radiotherapeutic agents. For in vivo administration, a radiopharmaceu-tical compound of the invention may be provided in apharmaceutical composition. As used herein, the term "pharmaceutical composition" refers broadly to a compo- sition comprising or consisting of a radiopharmaceutical compound of the present invention and one or more phar-maceutically acceptable components such as carrier so-lutions, adjuvants and / or excipients. Preferably, thecomponents are sterile. It is to be understood that any reference in the present description to the administration of a ra- diopharmaceutical compound of the invention also in- cludes administration of a pharmaceutical compositioncomprising said radiopharmaceutical compound even if thelatter is not specifically mentioned. As used herein, the term "pharmaceutically ac-ceptable” refers to a material that is suitable for invivo administration to a subject, preferably a humansubject, without undue adverse side effects such as tox- icity, significant irritation and / or allergic re- sponses. In other words, the benefit / risk ratio must be reasonable. In some embodiments, the radiopharmaceuticalsare provided in a pharmaceutically acceptable solution.Suitable solutions include, but are not limited to,buffers, such as phosphate buffered saline (PBS), salineand other isotonic aqueous buffer solutions such asRinger’s solution. Suitable additives include, but arenot limited to, preservatives (e.g. ascorbic acid, pro- pylene glycol) and pH-adjusting agents. Preferably, the pharmaceutical composition ac- cording to the present invention is in the form of an injectable composition. More preferably, the pharmaceu- tical composition is in the form intended for intrave- nous administration. Depending on the need of customers, the amount of radioactivity in the end product can be up to, but not limited to 100 GBq. The present invention also provides compounds, more specifically precursor compounds, having a generalformula (II) XPis nitrogen or carbon; R1Pis selected from the group consisting of hydroxyl, amino, amide, dexamethasone, alkyl ester, phe- nyl ester, and polyethylene glycol amide; R2Pis selected from the group consisting of hydrogen, and riboside; R3Pis selected from the group consisting of trimethylammonium trifluoroacetate, trimethylammoniumacetate, and trimethylammonium trifluoromethanesul-fonate, when R4Pis selected from the group consisting of methyl, ethyl, and hydroxyl; or R3Pis selected from the group consisting of methyl, ethyl, and hydroxyl, when R4Pis selected fromthe group consisting of trimethylammonium trifluoroace-tate, trimethylammonium acetate, and trimethylammonium trifluoromethanesulfonate; or R3Pand R4Pare both selected, independentlyfrom each other, from the group consisting of trime-thylammonium trifluoroacetate, trimethylammonium ace-tate, and trimethylammonium trifluoromethanesulfonate.The alkyl ester is as defined for the generalFormula (I) above.In an embodiment, the precursor compound is 6- (trimethyl-λ4-azaneyl)nicotinic acid trifluoromethane- sulfonate, i.e. a compound having the formula: . In an embodiment, the precursor compound is 6- (trimethyl-λ4-azaneyl)nicotinamide trifluoromethane- sulfonate, i.e. a compound having the formula: . In an embodiment, the precursor compound is 6- (trimethyl-λ4-azaneyl)nicotinamide riboside trifluoro- methanesulfonate, i.e. a compound having the formula: . Compounds of the general formula (II) may be used as precursors for the present radiopharmaceuticals.Accordingly, also provided is a method for the prepara-tion of the present radiopharmaceutical compounds fromthe precursor compounds using means and methods wellknown in the art. In the method the precursor compoundsare incubated with [18F]fluoride, iodine or astatineisotopes or their complex in a suitable solvent (e.g. acetonitrile) for a sufficient time, such as up to 30min, at a suitable temperature (e.g. 60 oC). When nec-essary, additives (e.g. ascorbic acid) may be includedin the reaction mixture. Then the product is purified with solid phase extraction or high performance liquidchromatography or other suitable means. The end productis formulated in a suitable vehicle including, but notlimited to, phosphate-buffered saline or saline, usingmeans and methods readily available in the art. Thepreparation of the radiopharmaceuticals may be done us-ing any suitable devices or systems including home-madedevices or commercially available devices (e.g. TrasisAllinOne). Quality control may be done with any suitablemeans including, but not milted to, high performanceliquid chromatography or thin-layer chromatography. Forany radiopharmaceutical compound to be prepared, a cor-responding cold compound, i.e. a compound in which a radioisotope is replaced with a corresponding non-radi- oactive isotope of fluorine, iodine or astatine, may be used as a reference compound for quality control or any other purpose. Alternative and / or further particulars for the preparation method of the present pharmaceuticals are readily understood by those skilled in the art. In accordance with what is disclosed above, thepresent invention also provides use of a compound having a general Formula (III): wherein: XRis nitrogen or carbon; R1Ris selected from the group consisting of hydroxyl, amino, amide, dexamethasone, alkyl ester, phe- nyl ester, and polyethylene glycol amide; R2Ris hydrogen or riboside; R3R is hydrogen, alkyl, or non-radioactive flu-orine or iodine;R4R is hydrogen, alkyl, or non-radioactive flu-orine or iodine;with the proviso that least one of R3Rand R4Ris non-radioactive fluorine or iodine,as a reference compound for a corresponding radiopharmaceutical having general formula (I), whereinX, R1, R2, R3 and R4 are as described above. The referencecompounds may be used as quality controls for the cor-responding radiopharmaceutical compounds or for anyother purpose as desired. The alkyl ester and alkyl are as defined for the general Formula (I) above. Also provided is a kit for the preparation of a radiopharmaceutical according to the present inven- tion, the kit comprising a corresponding precursor com- pound of general Formula (II), a radioisotope of fluo-rine, iodine or astatine, and optionally a correspondingreference compound of general Formula (III). More specifically, provided is a kit for the preparation of a radiopharmaceutical compound of general Formula wherein: X is nitrogen or carbon; R1is selected from the group consisting of hydroxyl, amino, amide, dexamethasone, alkyl ester, phe- nyl ester, and polyethylene glycol amide; R2is hydrogen or riboside; R3 is a radionuclide, hydrogen, or alkyl;R4is a radionuclide, hydrogen, or alkyl; with the proviso that least one of R3and R4is a radionuclide; the kit comprising: (i) a precursor compound of general Formula(II): wherein XP is the same as X; R1P is the same R1; R2Pis the same as R2; R3Pis selected from the group consisting of trimethylammonium trifluoroacetate, tri- methylammonium acetate and trimethylammonium trifluoro-methanesulfonate, if R3 is a radionuclide, R4P then beingselected from the group consisting of methyl, ethyl, and hydroxyl; or R3Pis selected from the group consisting of methyl, ethyl and hydroxyl, if R4is a radionuclide, R4Pthen being selected from the group consisting of trimethylammonium trifluoroacetate, trimethylammoniumacetate and trimethylammonium trifluoromethanesul-fonate; or R3Pand R4Pare both selected, independentlyfrom each other, from the group consisting of trime-thylammonium trifluoroacetate, trimethylammonium ace-tate, and trimethylammonium trifluoromethanesulfonate,if R3 and R4 are both radionuclides; and(ii) one or more radioisotopes correspondingto the radionuclide of R3 and / or R4. In some embodiments, the kit may also comprise: (iii) a reference compound of general Formula (III): wherein: wherein XRis the same as X, R1Ris the same R1, R2Ris the same as R2, R3Ris hydrogen if R3is hydrogen, R3Ris a corresponding non-radioactive isotope if R3is a radionuclide; R4Ris hydrogen if R4is hydrogen, R4Ris a corresponding non-radioactive isotope if R4is a ra- dionuclide. To illustrate this aspect, without limitation, if the radiopharmaceutical compound to be prepared is, for example, [18F]niacin, the precursor compound to be included in the kit may be 6-trimethyl-λ4-azaneyl)nic- otinamide trifluoromethanesulfonate, and the radioiso- tope also to be included may be fluorine-18. If in- cluded, a reference compound in this case would be non- radioactive niacin.Example 1. Preparation of [18F]niacinIn-house produced [18F]fluoride (3.8−5.2 GBq) was extracted onto a Sep-Pak Accell Plus QMA Plus Light anion-exchange cartridge (QMA; Waters, Milford, MA, USA), which was preconditioned with 0.5 M aqueous po- tassium carbonate (2 mL) and water (5 mL) (TraceSELECT Honeywell, Charlotte, NC, USA). Elution of [18F]fluoride was carried out using a solution of Kryptofix 2.2.2 (9.2 mg, 23.1 µmol) and potassium carbonate (1.6 mg, 15.4 µmol) in Milli-Q water (76.9 µL) and acetonitrile (1.9 mL).16The eluate was then dried under nitrogen flow at 120 °C, followed by the addition of the precursor com- pound N,N,N-trimethyl-5-((4-nitrophenoxy)carbonyl)pyr- idin-2-aminium trifluoromethanesulfonate (10.0 mg, 22.2 µmol) in 0.8 mL acetonitrile. The reaction mixture was maintained at 37 °C for 10 min and then diluted with water (1.0 mL). The intermediate compound 6-[18F]fluo- ronicotinic acid 4-nitrophenyl ester was purified using HPLC equipped with a radioactivity detector and a re- versed-phase C18 column (Jupiter Proteo, 250×10 mm, 5 µm, 90 Å; Phenomenex, Torrance, CA, USA) at a flow rate of 4 mL / min. Solvent A was 0.1% trifluoroacetic acid (TFA) in water, while solvent B was 0.1% TFA in ace- tonitrile. The HPLC elution gradient was from 45 to 70% B during 0–13 min. The HPLC fraction containing 6- [18F]fluoronicotinic acid 4-nitrophenyl ester was col- lected and diluted with 30 mL of water, and the product was extracted onto an Oasis HLB Plus Light cartridge (Waters, Milford, MA, USA). Compound 6-[18F]fluoronico- tinic acid 4-nitrophenyl ester was then hydrolyzed by adding 1M NaOH (0.58 mL) directly onto the HLB car- tridge. NaOH was kept in the cartridge for 10 min afterwhich [18F]niacin was eluted from the cartridge with 2mL of water into a vial containing 2M HCl (0.14 mL) and 2M phosphoric acid (0.125 mL). After synthesis, theidentity and radiochemical purity of [18F]niacin was ex-amined using HPLC. 0.5−0.8 MBq of [18F]niacin was in-jected into a C18 reversed-phase column (Jupiter Proteo, 250 × 4.6 mm, 5 µm, 90 Å; Phenomenex). The results were then compared to cold reference HPLC results, where 20- 50 nmol of commercial 6-fluoronicotinic acid in water was used. Solvent A consisted of 0.1% TFA in water, while solvent B contained 0.1% TFA in acetonitrile. The HPLC elution gradient began at 10% B and ended at 50% B between 0−10 min, at a flow rate of 1.5 mL / min, and wasmonitored by radioactivity detection and UV detectionat a wavelength of 220 nm and 254 nm. More generally, the radiosynthesis was done in a two-step synthesis where in the first step prosthetic group 6-[18F]fluoronicotinic acid 4-nitrophenyl ester was prepared using nucleophilic fluorination with the industry standard [K / K2.2.2]+ 18F- complex. Then, the es- ter in 6-[18F]fluoronicotinic acid 4-nitrophenyl esterwas hydrolyzed into [18F]niacin by adding 1M NaOH di-rectly onto the solid phase extraction (SPE)-cartridge, after which the formed product was eluted and collected into the end product vial containing 2M HCl and 2M phos- phoric acid to neutralize the NaOH. Final pH of the product was between 5–7.5. The decay-corrected radio- chemical yield was 38.1% ± 9.7 (n = 9) and the radio- chemical purity was 99.7% ± 0.6. The molar activity was 146.7 ± 63.6 GBq / µmol at the end of the synthesis. The total synthesis time was 112. ± 9.2 min, starting fromthe end of bombardment. The stability of [18F]niacin inthe final formulation was at least 4 h at room temper-ature (longer time was not tested.)An overall reaction scheme for the preparationof [18F]niacin is shown in Figure 1.Example 2. General preparation procedure for [131I]nia-cin, [123I]niacin and other iodinated compoundsAll the iodinated compounds were prepared with precursors bearing a suitable activation group of tribu- tylstannyl functionality or boronic esters. Here is a specific example to demonstrate the synthesis prodecure. Precursor compound 6-tributylstynnyl nicotinic acid 4- nitrophenyl ester (1 mg) was dissolved in a mixture of 100 μL dimethyl sulfoxide (DMSO), 5 μL acetic acid, 20 μL phosphate-buffered saline (PBS, pH=7.4) containing 2 mg chloramine-T. 100 MBq of [131I]NaI in 0.1 M NaOH (15 μL) was added. The reaction mixture was kept at room temperature for 15 minutes, and it was quenched with a solution of sodium metabisulfite (1.0 M, 20 μL). The reaction mixture was diluted in 25 ml water and the reaction intermediate was bound onto two HLB cartridges tandemly connected together. Then reaction intermediate was hydrolyzed on-cartridge by slowly passing 1.0 M NaOH (580.0 μL) through the HLB cartridges. NaOH solution was kept in the cartridge for 10 min, after which the final product was eluted from the cartridge with 2.0 mL of water into a vial containing 2.0 M HCl (140.0 μL) and 2.0 M phosphoric acid (125.0 μL).Example 3. General preparation procedure for [211At]ni-acin and other astatinated compounds All the astatinated compounds were prepared with precursors bearing a suitable activation group of tributylstannyl or trimethylstannyl functionality. Here is a specific example to demonstrate the synthesis prodecure. Precursor compound 6-tributylstynnyl nico- tinic acid (10 μg) was added to a solution of 70 MBq211At-radionuclide in a solution of methanol containing 1% acetic acid and 1.0 mg N-iodosuccinimide. The reac- tion was kept at room temperature for 2 minutes, and the final product was purified by semi-preparative high- performance liquid chromatography with 7% of EtOH in phosphate-buffered saline.Example 4. In vivo detection of glioblastoma by PETimaging All animal work was approved by the National Project Authorization Board in Finland with permissionnumber of ESAVI / 10262 / 2022 and ESAVI / 3630 / 2023, and werecarried out in compliance with the EU Directive 2010 / EU / 63 on the protection of animals used for scien- tific purposes. Statistical analyses were performed with GraphPad Prism, version 6. Results were expressed as mean ± standard deviation (SD). Unpaired Student t-test- ing was applied to measure the differences between in-dependent datasets. P values of less than 0.05 wereconsidered statistically significant. Glioblastoma mouse model preparation Glioblastoma BT12-KUH cells were originated from a patient with glioblastoma and the tumor tissue sample was taken in Kuopio University Hospital, Finland, in 2011. To differentiate this cell line from the com- mercial BT12 cell lines, our cell line was named as BT12-KUH and KUH denoted Kuopio University Hospital. The generation and cultivation of BT12-KUH were describedpreviously [1]. Briefly, immunocompromised female mice(Rj: NMRI-FOXn1nu / nu strain, 6-7 weeks old, JanvierLabs, France) were intracranially engrafted with BT12- KUH cells. The glioblastoma cells (105) in 5 µL 0.9% saline were inoculated into the right hemisphere of mouse brain with Hamilton syringe using a stereotaxic machine (World Precision Instruments, FL 34240, USA). After the surgery, mice were given pain killers for 2 days and their wellbeing was monitored daily. At day 21- 23 post cell-inoculation, the mice with glioblastoma were used for PET imaging and other studies.PET imaging, ex vivo biodistribution and autoradiography(ARG) PET imaging was performed in combination with high-resolution computed tomography (HRCT) for anatom- ical reference on a small-animal imaging instrument Molecubes (Molecubes NV, Belgium) for mice. During the whole imaging procedure, animals were under anesthesia with continuous inhalation of isoflurane. The animals were first imaged with HRCT for 6 min, and then injectedwith [18F]niacin (3-5 MBq per mouse) or [11C]methionine(4-5 MBq) or the glucose analogue [18F]FDG intravenously(i.v.) from tail vein via a cannulation, and imaged with PET in dynamic mode for 60 min. The use of the clinicalradiotracer [11C]methionine and [18F]FDG were for com-parison purposes with [18F]niacin. Two mice were imaged at a time and the acquisition time frames were 6 × 10 s, 4 × 60 s, 5 × 300 s, 3 × 600 s. At the end of imaging, mice were euthanized under deep anesthesia by cardiac puncture from left ventricle. Subsequently, the mice were perfused with 10 mL PBS from the left ventricle.In the in vivo blocking experiments, the imaging proce-dures were the same as described above except that the mice were i.v. administrated with AZD3965 (1.1 mg / kg ofbodyweight), mepenzolate bromide (5 mg / kg of bodyweight)or niacin (10 mg / kg of bodyweight) from tail veil beforethe administration of [18F]6-fluoronicotinic acid. PET images were reconstructed with an ordered subsets ex- pectation maximization 3-dimentional algorithm (OSEM- 3D) and CT was reconstructed using soft tissue algo-rithm. PET / CT data were analyzed with the Carimas 2.10software (Turku PET Centre, Finland, www.turkupetcen- tre.fi / carimas / ). Regions of interest (ROI) were drawn with the spline tool either referring to the anatomical CT image (whole tissues) or to the focal maximum (tumor) and minimum (healthy brain) intensities in the brain PET. Quantitative analyses were performed to the defined ROIs to obtain standardized uptake values (SUV) and time-activity curves (TAC). Correct ROI placement was confirmed by transaxial and sagittal views. SUV was nor- malized for the injected radioactivity dose and animal body weight. After PET imaging and euthanasia, tissue sam- ples were collected and counted with a Wizard gamma-counter (Wallac Oy, Turku, Finland). The measured radi-oactivity was normalized with injected dose per animal weight, the weights of the tissue samples, and radioac- tivity decay. The measurements were corrected for re- sidual radioactivity of the tail and the cannula. The results were expressed as percentage of the injecteddose per gram of tissue (%ID / g). Mice brains were snap-frozen in isopropane cooled with dryice and prepared as cryosections with thicknesses of 20 µm and 10 µm. The cryosections were thaw-mounted onto microscopy glass slides and exposed to a phosphor imaging plate (Fuji- film) overnight inside a lead shielding. Digital auto- radiography was performed with a BAS-5000 scanner. The results were expressed as photo-stimulated luminescence per square millimeter (PSL / mm2). ARG images were ana-lyzed with Carimas software. As shown in Figure 2, theglioblastoma tumor was clearly visualized with extraor- dinary imaging performance (Fig. 2A and 2B). In the presence of AZD3965 as the inhibitor of monocarboxylate transporter 1 (MCT1), the tumor uptake was completelyblocked (Fig. 2C). In the healthy mice as control group,there was not any focal uptake in the brain (Fig. 2D). The blocking effect was also shown in the time-activity curves (TACs) in Figure 2E. The TACs clearly showed that the MCT1 blocking effects. MCT1 is a crucial transporter in cancers in general, and [18F]niacin and the related compounds will be useful to probe MCT1 expression and in the new drug development for MCT1-targeted therapy. In the case of GPR109A blocking (Fig. 2E), reduced tumor uptake was observed, which suggests that [18F]niacin has interactions with GPR109A. In the clinical PET imaging procedures, fasting causes extra challenges in the clin- ical practice and patients may feel uncomfortable. We have confirmed that fasting is not necessary in the use of [18F]niacin for PET imaging (Fig. 2F). This is a clear advantage over the current clinical radiopharmaceuti- cals including [18F]FDG. Most importantly, [18F]niacin showed much better and extraordinary PET imaging per-formance compared to the current clinical radiopharma-ceuticals [11C]methionine and [18F]FDG (Fig. 3). Thisopens new perspectives for clinical glioma diagnosis and therapy, and for monitoring treatment-responses in new drug development. The use of [11C]methionine and [18F]FDG causes lots of false-positive signals in the brain, which makes diagnosis extremely challenging. Ex vivo biodistribution in various organs andtissues was shown in Figure 4. The data showed that the biodistribution patterns were favorable, and the radi- oactivity uptake in critical organs were low. Im- portantly, the bone uptake was negligible indicatingthat the in vivo defluorination did not take place. Thiswas in line with the observed excellent in vivo stabil- ity that we observed with plasma analysis. In addition, we have observed focal and intense signals in autoradi- ography with brain tumor tissue samples from mice with glioblastoma (Figure 5). Tumor uptake and radiopharmacokinetics of [18F]niacin [18F]niacin was administrated intravenouslyinto mice via tail vein for PET imaging in a dynamic mode for 60 minutes, and the intracranial glioblastomawas clearly visualized (Fig. 2, panels A and B). Incontrast, the skull bone and other tissues in the head had low intensity of radioactivity. In the sagittal view of the brain images (Fig. 2, panel B), it was visible that the tumor had a little extension outside of the skull. That was due to the tumor growth through the hole, which was made through the skull in the process of tumor cell inoculation. In the presence of the in- hibitor of monocarboxylate transporter 1 (MCT1), AZD3965 (1.1 mg / kg), the brain and tumor uptake was diminished (Fig. 2, panel C). In healthy mice as controls, there was no focal uptake observed in the brain (Fig. 2, panel D). As indicated by the time-activity curve (TAC, Fig.2, panel E), [18F]niacin accumulated into the tumorwithin 10 minutes after it was injected to the blood stream, and was slowly cleared out during next 50 minutes of observation. In the MCT1 blocking experi- ments, the TAC remained flat all through the 60 min imaging, indicating that the radioactivity did not enter the tumor () and MCT1 was a critical transporter. In thepresence of mepenzolate bromide (5 mg / kg) as an inhib-itor of GPR109A, tumor uptake of [18F]niacin was lowerthan the unblocked experiments at all the time points during a 60 min duration of PET imaging. Additionally, we have quantified the biokinet-ics of [18F]niacin in various of organs and tissues, forexample in heart, lung, blood and liver (Figure 6). This data is important to indicate the dynamics of [18F]niacin uptake in the organs along with time.Blood radioactivity analysis and in vivo stability of[18F]niacin At the end of PET imaging (60 min post-injec- tion), blood samples were collected from mice into hep- arinized tubes. Blood cells and plasma were isolated by centrifugation (2,100 × g) for 5 min. Plasma proteins were precipitated by adding equal volume of acetonitrile and pelleted by centrifugation (14,000 × g for 2 min) at r.t. Plasma supernatant was removed to a separate tube. The radioactivity of the isolated blood components was measured with a Wizard gamma-counter (, PerkinElmer, Turku). Plasma supernatant samples were analyzed by HPLC equipped with a radioactivity detector. The analysis was done on a reversed-phase C18 column (Phenomenex, JupiterProteo, 250 × 10 mm, 5 µm, 90 Å) at flow rate of5 mL / min. Solvent A was 0.1% TFA in water and solvent Bwas 0.1% TFA in acetonitrile. The HPLC elution gradientwas during 15 min from 10% B to 50% B. The results showedthat [18F]niacin has favorable distribution patternsamong the blood components. The in vivo stability of [18F]niacin is perfect (Fig. 7). During one hour circu- lation in mice, >99% of intact [18F]niacin was observed (Fig. 7B), and the reference compound was used in the high performance liquid chromatographic analysis (Fig. 7A).Example 5. In vivo detection of brain metastases by PETimaging All animal work was approved by the National Project Authorization Board in Finland with permissionnumber of ESAVI / 3630 / 2023, and was carried out in com-pliance with the EU Directive 2010 / EU / 63 on the protec- tion of animals used for scientific purposes. Preparation of mouse model with human breast cancer brain metastasis Immunodeficient female mice (Rj: NMRI- FOXn1nu / nu strain, 5-6 weeks old, Janvier Labs, France) were engrafted with human-derived triple-negative breast cancer i231-BrM2 cells (2 × 105cells per animal) intracranially. Briefly, the cells in 5 µL 0.9% saline were inoculated into the right hemisphere of the mouse brain with a Hamilton syringe using a stereotaxic ma- chine (World Precision Instruments Sarasota, FL, USA). The inoculation site was 2 mm from the bregma and 2.5 mm deep into the brain parenchyma. The mouse was placed under 3% isoflurane anesthesia and kept warm at 37 °C using the heating plate and the rectal heating probe connected to a temperature control system (World Preci- sion Instrument) throughout the procedure. Mice were administered with 3 µg / mL Buprenorphine pain killer and 5 mg / kg Caprofen before and after intracranial implan- tation, respectively, and continued for two days post- operation. Breast cancer brain metastasis PET imaging with [18F]ni- acin PET and high-resolution computed tomography (HRCT) imaging were carried out using Molecubes small- animal PET and CT imaging systems (Molecubes NV, Gent, Belgium). Mice were provided with food and tap water adlibitum prior to the PET study. During the whole imagingprocedure, mice were on a heating pad under anesthesia with continuous inhalation of 1─2% isoflurane. In a typ- ical procedure, HRCT was first performed for the mice without the use of contrast agents, and the mice werethen injected with [18F]niacin (5 MBq per mouse) intra-venously via tail vein with a cannula. Two mice were simultaneously imaged, with 60-minute dynamic PET data collected in list mode. PET data reconstruction utilized an OSEM-3D algorithm with time frames of 6 × 10 s, 4 × 60 s, 5 × 300 s, and 3 × 600 s, while CT reconstruction employed the iterative image space reconstruction algo- rithm (ISRA) method. PET / CT image analysis was conducted using Carimas 2.10 software. Regions of interest (ROIs) were defined using the spline tool, referencing either anatomical CT images or focal maxima in brain PET im- ages. As shown in Figure 8, human-derived triple-negative breast cancer brain metastasis was clearly vis-ualized. This result demonstrates the potential of thepresent radiopharmaceutical compounds as radiotracersand radiopharmaceuticals for imaging and treating brainmetastases, respectively.Example 6. In vivo detection of liver metastasesAll animal work was approved by the National Project Authorization Board in Finland with permission number of ESAVI / 3630 / 2023, and was carried out in com- pliance with the EU Directive 2010 / EU / 63 on the protec- tion of animals used for scientific purposes. Preparation of mouse model with melanoma cancer liver metastasis Male C57BL / 6J or C57BL / 6N mice (7-10 weeks old, Janvier Labs, France) were injected via the tail vein with murine B16-Luc melanoma cells (1.8 × 105cells per animal). At day 5 post-injection of tumor cells, liver metastasis will be large enough for imaging studies. When necessary, tumor growth can be followed by biolu- minescence imaging.Melanoma liver metastasis PET imaging with [18F]niacinThis PET imaging study was performed similarlyas described for Example 5 above.As shown in Figure 9, melanoma liver metastasiswas clearly visualized. This result demonstrates the potential of the present radiopharmaceutical compounds as radiotracers and radiopharmaceuticals for imaging and treating cancers, respectively. It is obvious to a person skilled in the art that with the advancement of technology, the basic idea of the invention may be implemented in various ways. The invention and its embodiments are thus not limited to the examples described above, instead they may vary within the scope of the claims.

Claims

CLAIMS 1. A radiopharmaceutical compound or a pharma- ceutically acceptable salt thereof for use in treatingor preventing cancer, the radiopharmaceutical compoundhaving the general formula (I):(I) wherein X is nitrogen or carbon; R1is selected from the group consisting of hydroxyl, amino, amide, dexamethasone, alkyl ester, phe- nyl ester, and polyethylene glycol amide; R2 is hydrogen or riboside;R3 is a radionuclide, hydrogen, or alkyl;R4 is a radionuclide, hydrogen, or alkyl;with the proviso that at least one of R3 and R4is a radionuclide, andwith the proviso that if X is nitrogen and R1 is amide, said cancer is not melanoma.

2. The radiopharmaceutical compound or the pharmaceutically acceptable salt therefor for use ac- cording to claim 1, wherein R3is a radionuclide, pref-erably fluorine-18 or astatine-211, and R4 is hydrogen;or R3is hydrogen and R4is a radionuclide, preferablyfluorine-18 or astatine-211.

3. The radiopharmaceutical compound or thepharmaceutically acceptable salt thereof for use ac-cording to claim 2, wherein the radiopharmaceutical is selected from the group consisting of:[18F]nicotinic acid, [18F]nicotinamide, 6-[18F]fluoronicotinamide riboside, 5-[18F]fluoronicotinic acid, 5-[18F]fluoronicotinamide, 5-[18F]fluoronicotinamide riboside, 3-[18F]fluoro-4-methylbenzoic acid, [18F]fluorodexamethasone, 6-[18F]fluoro-5-methylnicotinate, methyl 6-[18F]fluoro-5-methylnicotinate, 6-([18F]fluoro)-N-(14-phenyl-3,6,9,12-tetrao- xatetradecyl)nicotinamide, [211At]astatonicotinic acid, [211At]astatonicotinamide, 6-[211At]astatonicotinamide riboside, 5-[211At]astatonicotinic acid, 5-[211At]astatonicotinamide, 5-[211At]astatonicotinamide riboside, 3-[211At]astato-4-methylbenzoic acid, [211At]astatodexamethasone, 6-[211At]astato-5-methylnicotinate, methyl 6-[211At]astato-5-methylnicotinate, 6-([211At]astato)-N-(14-phenyl-3,6,9,12- tetraoxatetradecyl)nicotinamide.

4. The radiopharmaceutical compound or thepharmaceutically acceptable salt thereof for use ac- cording to claim 1, wherein R3is selected from the group consisting of iodine-131, iodine-125, iodine-123, io- dine-124, and astatine-211, and R4is hydrogen; or R3is hydrogen and R4is selected from the group consisting of iodine-131, iodine-125, iodine-123, iodine-124, and as- tatine-211.

5. The radiopharmaceutical compound or the pharmaceutically acceptable salt thereof for use ac- cording to claim 1 or 4, with the proviso that R4is not iodine-123, when R1is hydroxyl and R2is hydrogen.

6. The radiopharmaceutical compound or the pharmaceutically acceptable salt thereof for use ac- cording to any one of claims 1, 4 or 5, wherein the radiopharmaceutical is selected from the group consist- ing of: 6-[131I]iodonicotinic acid, 6-[131I]iodonicotinamide, 6-[131I]iodonicotinamide riboside, 6-[123I]iodonicotinic acid, 6-[124I]iodonicotinic acid, 6-[125I]iodonicotinic acid, 6-[123I]iodonicotinamide, 6-[124I]iodonicotinamide, 6-[125I]iodonicotinamide, 6-[123I]iodonicotinamide riboside, 6-[124I]iodonicotinamide riboside, 6-[125I]iodonicotinamide riboside, 5-[123I]iodonicotinic acid, 5-[124I]iodonicotinic acid, 5-[125I]iodonicotinic acid, 5-[123I]iodonicotinamide, 5-[124I]iodonicotinamide, 5-[125I]iodonicotinamide, 5-[123I]iodonicotinamide riboside, 5-[124I]iodonicotinamide riboside, 5-[125I]iodonicotinamide riboside, 6-[211At]astatonicotinic acid, 6-[211At]astatonicotinamide, 6-[211At]astatonicotinamide riboside, 5-[211At]astatonicotinic acid, 5-[211At]astatonicotinamide, and 5-[211At]astatonicotinamide riboside.

7. The radiopharmaceutical compound or the pharmaceutically acceptable salt thereof for use ac- cording to any one of claims 1-6, wherein the radio-pharmaceutical is a tracer for a nuclear imaging tech- nique, preferably position emission tomography (PET) orsingle-photon emission computed tomography (SPECT).

8. The radiopharmaceutical compound or the pharmaceutically acceptable salt thereof for use ac- cording to claim 7, wherein the tracer is for imaging glioma, glioblastoma, brain metastasis, breast cancer, colon cancer, lung cancer, prostate cancer, ovarian can- cer, cell carcinoma, gastrointestinal stromal tumors, head and neck cancer, melanoma, liver cancer, bladder cancer, or testicular cancer.

9. The radiopharmaceutical compound or the pharmaceutically acceptable salt thereof for use ac- cording to any one of claims 1-6, wherein the radio- pharmaceutical is a radiotherapeutic agent.

10. The radiopharmaceutical compound or the pharmaceutically acceptable salt thereof for use ac- cording to claim 9, wherein the radiotherapeutic agent is for use in the treatment of glioma, glioblastoma, brain metastasis, breast cancer, colon cancer, lung can- cer, prostate cancer, ovarian cancer, cell carcinoma, gastrointestinal stromal tumors, head and neck cancer, melanoma, liver cancer, bladder cancer, or testicularcancer.

11. A radiopharmaceutical compound having the general Formula (I):X is nitrogen or carbon; R1is selected from the group consisting of hydroxyl, amine, dexamethasone, alkyl ester, phenyl es- ter, and polyethylene glycol amide; R2 is hydrogen or riboside;R3is a radionuclide, hydrogen, or alkyl; R4is a radionuclide, hydrogen, or alkyl; with the proviso that at least one of R3and R4is a radionuclide, with the proviso that when X is carbon, R1 is not hydroxyl, and with the proviso that the alkyl ester of R1 is not ethyl ester, when R3 is radionuclide and R4 is hy- droxyl or pharmaceutically acceptable salt thereof.

12. The radiopharmaceutical compound according to claim 11, wherein R3is a radionuclide, preferablyfluorine-18 or astatine-211, and R4 is hydrogen; or R3is hydrogen and R4is a radionuclide, preferably fluo-rine-18 or astatine-211.

13. The radiopharmaceutical compound according to claim 12, wherein the radiopharmaceutical is selected from the group consisting of: [18F]nicotinic acid, [18F]nicotinamide, 6-[18F]fluoronicotinamide riboside, 5-[18F]fluoronicotinic acid, 5-[18F]fluoronicotinamide, 5-[18F]fluoronicotinamide riboside, 3-[18F]fluoro-4-methylbenzoic acid, [18F]fluorodexamethasone, 6-[18F]fluoro-5-methylnicotinate, methyl 6-[18F]fluoro-5-methylnicotinate, 6-([18F]fluoro)-N-(14-phenyl-3,6,9,12-tetrao- xatetradecyl)nicotinamide, [211At]astatonicotinic acid, [211At]astatonicotinamide,6-[211At]astatonicotinamide riboside, 5-[211At]astatonicotinic acid, 5-[211At]astatonicotinamide, 5-[211At]astatonicotinamide riboside, 3-[211At]astato-4-methylbenzoic acid, [211At]astatodexamethasone, 6-[211At]astato-5-methylnicotinate, methyl 6-[211At]astato-5-methylnicotinate, 6-([211At]astato)-N-(14-phenyl-3,6,9,12- tetraoxatetradecyl)nicotinamide.

14. The radiopharmaceutical compound according to claim 11, wherein R3is selected from the group con- sisting of iodine-131, iodine-125, iodine-123, iodine- 124, and astatine-211, and R4 is hydrogen; or R3 is hydrogen and R4is selected from the group consisting of iodine-131, iodine-125, iodine-123, iodine-124, and as- tatine-211.

15. The radiopharmaceutical compound accordingto claim 11 or 14, with the proviso that R4 is notiodine-123, when R1is hydroxyl and R2is hydrogen.

16. The radiopharmaceutical compound according to any one of claims 11, 14 or 15, wherein the radio- pharmaceutical is selected from the group consisting of: 6-[131I]iodonicotinic acid, 6-[131I]iodonicotinamide, 6-[131I]iodonicotinamide riboside, 6-[123I]iodonicotinic acid, 6-[124I]iodonicotinic acid, 6-[125I]iodonicotinic acid, 6-[123I]iodonicotinamide, 6-[124I]iodonicotinamide, 6-[125I]iodonicotinamide, 6-[123I]iodonicotinamide riboside, 6-[124I]iodonicotinamide riboside, 6-[125I]iodonicotinamide riboside, 5-[123I]iodonicotinic acid, 5-[124I]iodonicotinic acid,5-[125I]iodonicotinic acid, 5-[123I]iodonicotinamide, 5-[124I]iodonicotinamide, 5-[125I]iodonicotinamide, 5-[123I]iodonicotinamide riboside, 5-[124I]iodonicotinamide riboside, 5-[125I]iodonicotinamide riboside, 6-[211At]astatonicotinic acid, 6-[211At]astatonicotinamide, 6-[211At]astatonicotinamide riboside, 5-[211At]astatonicotinic acid, 5-[211At]astatonicotinamide, and 5-[211At]astatonicotinamide riboside.

17. The radiopharmaceutical compound according to any one of claims 11-16, wherein the radiopharmaceu- tical is a tracer for a nuclear imaging technique, pref-erably position emission tomography (PET) or single-photon emission computed tomography (SPECT).

18. The radiopharmaceutical compound or the pharmaceutically acceptable salt thereof for use ac- cording to claim 7, wherein the tracer is for imaging glioma, glioblastoma, brain metastasis, breast cancer, colon cancer, lung cancer, prostate cancer, ovarian can- cer, cell carcinoma, gastrointestinal stromal tumors, head and neck cancer, melanoma, liver cancer, bladder cancer, or testicular cancer.

19. The radiopharmaceutical compound according to any one of claims 11-16, wherein the radiopharmaceu- tical is a radiotherapeutic agent.

20. The radiopharmaceutical compound according to claim 19, wherein the radiotherapeutic agent is foruse in the treatment of glioma, glioblastoma, brain me-tastasis, breast cancer, colon cancer, lung cancer, prostate cancer, ovarian cancer, cell carcinoma, gas- trointestinal stromal tumors, head and neck cancer, mel-anoma, liver cancer, bladder cancer, or testicular can-cer.

21. A radiopharmaceutical composition compris-ing the radiopharmaceutical compound or a pharmaceuti-cally acceptable salt thereof as defined in any one ofclaims 1-20 in a pharmaceutically acceptable carriersolution.

22. A method for imaging a subject, the method comprising: administering the radiopharmaceutical compound or the pharmaceutically acceptable salt thereof as de-fined in any one of claims 1-20 or the radiopharmaceu-tical composition according to claim 21 to the subject;allowing the radiopharmaceutical to accumulatein tissues and organs of the subject; andproviding an image obtained by a nuclear imag-ing technique, preferably a PET or SPECT image, showing whether said accumulation has occurred or not.

23. The method according to claim 22, whereinaccumulation of the radiopharmaceutical compound in atissue or an organ of the subject is indicative of cancer or cancer metastasis.

24. The method according to claim 23, the can-cer is glioma, glioblastoma, brain metastasis, breastcancer, colon cancer, lung cancer, prostate cancer, ovarian cancer, cell carcinoma, gastrointestinal stro- mal tumors, head and neck cancer, melanoma, liver can-cer, bladder cancer, or testicular cancer.

25. The method according to claim 22 or 23, wherein accumulation of the radiopharmaceutical com- pound in the brain is indicative of glioma, preferably glioblastoma, or brain metastasis.

26. A precursor compound for the radiopharma-ceutical compound defined in any one of claims 1-20, theprecursor compound having a general formula (II):wherein XPis nitrogen or carbon; R1Pis selected from the group consisting of OH (hydroxyl), NH2 (amino, amide), dexamethasone, alkyl ester, phenyl ester, and polyethylene glycol amide; R2Pis selected from the group consisting of hydrogen, and riboside; and R3Pis trimethylammonium trifluoroacetate, tri-methylammonium acetate, and trimethylammonium trifluo-romethanesulfonate, when R4Pis selected from the group consisting of methyl, ethyl, and hydroxyl; or R3Pis selected from the group consisting of methyl, ethyl, and hydroxyl, when R4Pis selected fromthe group consisting of trimethylammonium trifluoroace-tate, trimethylammonium acetate, and trimethylammonium trifluoromethanesulfonate; or R3Pand R4Pare both selected, independentlyfrom each other, from the group consisting of trime-thylammonium trifluoroacetate, trimethylammonium ace-tate, and trimethylammonium trifluoromethanesulfonate.

27. Use of the compound according to claim 26 for the preparation the radiopharmaceutical as defined in any one of claims 1-20.

28. A method for the preparation of the radi- opharmaceutical compound as defined in any one of claims 1-20, the method comprising: contacting a precursor compound according to claim 26 with a radionuclide corresponding to the radi- onuclide in the radiopharmaceutical compound to be pre- pared;purifying the radiopharmaceutical compound so obtained; and formulating the purified radiopharmaceuticalcompound in a pharmaceutically acceptable carrier solu-tion.

29. The method according to claim 28, wherein the method includes confirming the identity of the ra- diopharmaceutical compound prepared using a correspond- ing non-radioactive reference compound.

30. Use of a compound having the general For- mula (III):wherein: XRis nitrogen or carbon; R1Ris selected from the group consisting of hydroxyl, amino, amide, dexamethasone, alkyl ester, phe- nyl ester, and polyethylene glycol amide; R2Ris hydrogen or riboside; R3R is hydrogen, alkyl, or non-radioactive flu-orine or iodine; R4R is hydrogen, alkyl, or non-radioactive flu-orine or iodine; with the proviso that least one of R3Rand R4Ris non-radioactive fluorine or iodine, as a reference compound for a corresponding radiopharmaceutical having general Formula (I), wherein X, R1, R2, R3and R4are as defined in claim 1.

31. A kit for the preparation of a radiophar-maceutical compound as defined in any one of claims 1- 6, the kit comprising: a precursor compound of general Formula (II) as defined in claim 26, one or more radioisotopes corresponding to theradionuclide of R3 and / or R4, andoptionally a reference compound of general For- mula (III) as defined in claim 30.