A kind of 140 Nd- 140 Pr generator separation 140 Pr's method

Abstract

The present invention discloses a method based on 140 Nd‑ 140 Pr generator separation 140 Pr method, which first prepares the complex 140 Nd / 140 Pr‑DOTP, then the complex 140 Nd / 140 Pr-DOTP was loaded onto an anion exchange column and separated through acid activation, pure water pre-rinsing, standing, and pure water rinsing. 140 Pr. This method implements 140 The process of Pr separation is simple, using pure water for elution. 140 Pr has no carrier, does not contain complexing molecules, and does not require further purification. The DOTP used is a common chemical reagent, and its cost is significantly lower than that of DOTATOC.

Description

Technical Field

[0001] The invention belongs to the technical field of radionuclide separation, and specifically relates to a method based on 140 Nd- 140 Pr generator separation 140 The method of Pr. Background Art

[0002] 140 Pr is a positron-emitting nuclide with a half-life of 3.4 min and a stable decay product. 140 Ce. 140 Pr is a lanthanide nuclide that can be used to label small molecules, monoclonal antibodies, and peptides through direct or indirect coordination methods to prepare a variety of 140 Pr-labeled radioactive drugs can be used for disease diagnosis through PET (Positron Emission Computed Tomography) imaging.

[0003] 140 The direct preparation of Pr is mainly through accelerator irradiation 140 Ce target, through 140 Ce(p,n) 140 Pr reaction 140 Pr. prepared by accelerator irradiation 140 Pr also needs to be separated by radiochemistry before it can be used for drug labeling. The radiochemical separation process consumes a lot of time. 140 The half-life of Pr is only 3.4 min, which limits the direct preparation of 140 Application of Pr in nuclear medicine.

[0004] 140 Nd / 140 Pr is a nuclide pair that can be prepared into a generator. 140 The half-life of Nd is 3.37 days, and it can decay by electron capture (EC = 100%) to generate 140 Pr. Although from the nuclear properties, through 140 Nd- 140 Preparation of Pr generator 140 Pr is relatively perfect, but since Nd and Pr are adjacent lanthanide elements with extremely similar physical and chemical properties, direct separation is very difficult. In 2007, KP Zhernosekov et al. reported the use of DOTATOC (DOTA-DPhe 1 -Tyr 3 -octreotide) complex 140 Nd, loaded onto a C-18 column with 1 × 10 -3M DTPA solution was used for elution to obtain a 140 Nd- 140 Pr generator, 1 ml 1 × 10 -3 M DTPA solution was eluted to obtain not less than 93% 140 Pr. 140 Nd- 140 The Pr generator utilizes the hot atomic effect, especially 140 Nd decays to 140 The "post-effect" of Pr is separated 140 Pr, the specific principle is: 140 Nd decays by electron capture to 140 Pr, electron capture leads to 140 The loss of electrons in the inner layer of Pr generates holes. Due to the Auger process, the electrons in the outer layer will fill the holes and cause more photons and electrons knocked out by photons to be emitted, finally making 140 Pr is highly ionized. 140 The positive charges accumulated by Pr are redistributed through the internal charges of the molecule in a very short time. The strong Coulomb repulsion between the positive charges inside the molecule causes Coulomb explosion, making the complex 140 The chemical bonds of the DOTA ring of Pr are broken, thus releasing 140 Pr. Complex 140 Nd DOTATOC has a higher affinity for C-18 columns, while 140 Pr-DTPA has a weak affinity for C-18 columns, and the difference in polarity makes 140 Pr is separated. However, the DOTATOC used in this method is expensive and the obtained 140 Pr-DTPA has high complex stability and is difficult to convert into 140 PrCl3 or 140 Pr(NO3)3 and other easily labeled forms are difficult to meet the needs of further application in scientific research institutions and clinical practice. Summary of the invention

[0005] In view of this, the present invention discloses a method based on 140 Nd- 140 PR generator separation 140 Pr method, which first prepares the complex 140 Nd / 140 Pr-DOTP, then the complex 140 Nd / 140 Pr-DOTP was added to the anion exchange column and separated through acid activation, pure water pre-rinsing, standing, and pure water rinsing. 140 Pr, this method has a simple process, the purity of the separated product is relatively high and the cost is low.

[0006] To achieve this purpose, the present invention adopts the following technical solutions: a 140 Nd- 140 Pr generator separation 140 The method of Pr, the method comprising:

[0007] S1: Preparation 140 Nd / 140 Complex of Pr and DOTP 140 Nd / 140 Pr-DOTP;

[0008] S2: 140 Nd / 140 Pr-DOTP is loaded onto an anion exchange column, and then activated with V1 volume of acid. After activation time t1, the anion exchange column is kept in an acidic environment, and then the anion exchange column is pre-eluted with pure water to remove excess acid;

[0009] S3: Let the anion exchange column stand for 140 Pr grows naturally, and is washed with pure water at intervals of t2. 140 Pr solution.

[0010] Preferably, in said S1, 140 Nd- 140 Pr is prepared by accelerator irradiation reaction and obtained after radiochemical separation; the type of accelerator irradiation reaction includes but is not limited to 141 Pr(p,2n) 140 Nd, 141 pr(d,3n) 140 Nd, 140 Ce( 3 He,3n) 140 Nd, 140 Ce( 4 He,4n) 140 Nd and nat Ce( 3 He, xn) 140 Nd.

[0011] Preferably, in said S1, 140 Nd- 140 The chemical form of Pr is: +3 valence water-soluble salt, including but not limited to 140 Nd / 140 PrCl3 and 140 Nd / 140 Pr(NO3)3.

[0012] Preferably, the complex in S1 140 Nd / 140 The preparation process of Pr-DOTP is as follows: first 140 Nd / 140 The Pr solution and the DOTP solution are mixed in a certain amount ratio to obtain a mixed solution, and then the pH value of the mixed solution is adjusted using acid and alkali. 140 Nd / 140 Pr reacts with DOTP to form a complex.

[0013] Preferably, the 140 Nd / 140 The molar ratio of Pr to DOTP is 1:1-1:1.1; the acid solution is HCl, and the alkali solution is NaOH; the certain pH value is 11±0.5; the reaction temperature of the complex reaction is 80-100°C, and the reaction time is 30-60min.

[0014] Preferably, in S2, the filling material of the anion exchange column includes but is not limited to anion exchange resin and acidic aluminum oxide.

[0015] Preferably, in S2, the acid includes but is not limited to HCl and HNO3, the concentration of the acid is 0.01-0.1M, and the volume V1 is sufficient to maintain the amount of hydrogen ion substances in the acid to be loaded onto the anion exchange column. 140 Nd / 140 The amount of the substance of the pr-DOTP complex is 10 to 100 times; the time t1 is 10 to 30 minutes; and the volume of the pure water is ≥ 2 times the column volume.

[0016] Preferably, in S2 and S3, the conductivity of pure water at 25° C. is less than 5.1 μS / cm.

[0017] Preferably, in S3, the ambient temperature of the anion exchange column is room temperature, and the time t2 is 30 min.

[0018] The beneficial effects of the present invention are: 140 Nd- 140 Pr generator separation 140 The Pr method mainly utilizes complex 140 Nd / 140 Pr-DOTP and products 140 The significant difference in the chemical valence state of Pr is achieved 140 Isolation of pr, where the raw material is complexed with DOTP 140 Nd- 140 Pr-DOTP is -5 valent, and the product 140 pr is +3 valence; this method achieves 140 The process of Pr separation is simple; this method uses pure water for elution.140 Pr has no carrier, does not contain complexing molecules, and does not require further purification; the DOTP used in this method is a common chemical reagent and has significantly lower costs than DOTATOC. DETAILED DESCRIPTION

[0019] Those skilled in the art will appreciate that the embodiments described herein are intended to help readers understand the principles of the present invention, and should be understood that the protection scope of the present invention is not limited to such specific statements and embodiments. Those skilled in the art can make various other specific variations and combinations that do not deviate from the essence of the present invention based on the technical revelations disclosed by the present invention, and these variations and combinations are still within the protection scope of the present invention.

[0020] The present invention is described in detail below with reference to specific embodiments.

[0021] A kind of 140 Nd- 140 Pr generator separation 140 The method of Pr, the method comprising:

[0022] First, prepare the 140 Nd / 140 Complex of Pr and DOTP 140 Nd / 140 Pr-DOTP. The specific process is: first 140 Nd / 140 The Pr solution and the DOTP solution were mixed at a molar ratio of 1:1-1:1.1 to obtain a mixed solution, and then the pH value of the mixed solution was adjusted to 11±0.5 using HCl and NaOH. 140 Nd / 140 Pr and DOTP undergo complexation reaction at a temperature of 80-100°C and a reaction time of 30-60 min. 140 Nd / 140 Pr is prepared by accelerator irradiation reaction and obtained after radiochemical separation; the type of accelerator irradiation reaction includes but is not limited to 141 Pr(p,2n) 140 Nd, 141 Pr(d,3n) 140 Nd, 140 Ce( 3 He,3n) 140 Nd, 140 Ce( 4 He,4n) 140 Nd and nat Ce( 3 He, xn) 140Nd.

[0023] Next, 140 Nd / 140 The Pr-DOTP complex is loaded onto an anion exchange column, the filling material of the anion exchange column includes but is not limited to anion exchange resin and acidic aluminum oxide, and then the anion exchange column is activated with V1 volume of acid for 10 to 30 minutes to keep the anion exchange column in an acidic environment, and then the anion exchange column is pre-eluted with pure water with a volume ≥ 2 times the column volume to remove excess acid; the acid here includes but is not limited to HCl and HNO3 with a concentration of 0.01-0.1M, and the volume V1 of the acid is the amount of hydrogen ion substances in the acid that can be loaded onto the anion exchange column. 140 Nd- 140 The amount of substance of the Pr-DOTP complex is 10 to 100 times; the conductivity of pure water is less than 5.1 μS / cm at 25°C.

[0024] Finally, the anion exchange column was left to stand at room temperature until 140 From Nd decay 140 Pr grows naturally, and is washed with pure water with a conductivity of less than 5.1 μS / cm at 25°C every 30 minutes. 140 pr solution, the above pure water rinse 140 The power source of Pr includes but is not limited to gravity, vacuum or peristaltic pump.

[0025] Example 1

[0026] S1: Preparation 140 Nd / 140 Complex of Pr and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylphosphonic acid) (DOTP) 140 Nd / 140 Pr-DOTP;

[0027] 140 Nd / 140 Pr is derived from accelerator irradiated natural cerium target through nat Ce( 3 He, xn) 140 Nd was prepared by reaction and separated by radiochemistry. 140 Nd / 140 The molar ratio of Pr to DOTP was 1:1.1, the reaction pH was adjusted to 11 with NaOH and HCl, the reaction temperature was 95°C, and the reaction time was 30 min;

[0028] S2: The result obtained in step S1 140 Nd / 140 Pr-DOTP takes about 2.6×10 -9mol(in 140 Nd / 140 Pr calculation) was loaded onto an acidic alumina column, then activated for 15 min by adding 1 ml of 0.1 mM HCl, and then eluted with 3 column volumes of pure water;

[0029] S3: The anion exchange column treated in step S3 is allowed to stand at room temperature until 140 From Nd decay 140 pr grows naturally, and can be washed with pure water by gravity every 30 minutes or more. 140 Pr solution.

Claims

1. A method based on 140 Nd- 140 PR generator separation 140 The method of Pr is characterized in that The method comprises: S1: Preparation 140 Nd / 140 Complex of Pr and DOTP 140 Nd / 140 Pr-DOTP; S2: 140 Nd / 140 Pr-DOTP is loaded onto an anion exchange column, and then activated with V1 volume of acid. After activation time t1, the anion exchange column is kept in an acidic environment, and then the anion exchange column is pre-eluted with pure water to remove excess acid; S3: Let the anion exchange column stand for 140 Pr grows naturally, and is washed with pure water at intervals of t2. 140 Pr solution.

2. According to claim 1, based on 140 Nd- 140 Pr generator separation 140 The method of Pr is characterized in that The S1 140 Nd / 140 Pr is prepared by accelerator irradiation reaction and obtained after radiochemical separation; the type of accelerator irradiation reaction includes 141 pr(p, 2n) 140 Nd, 141 Pr(d,3n) 140 Nd, 140 Ce( 3 He,3n) 140 Nd, 140 Ce( 4 He,4n) 140 Nd and nat Ce( 3 He, xn) 140 Nd.

3. The method according to claim 2 140 Nd- 140 Pr generator separation 140 The method of Pr is characterized in that In S1, 140 Nd / 140 The chemical form of Pr is: +3 valence salt that is easily soluble in water, including 140 Nd / 140 PrCl3 and 140 Nd / 140 Pr(NO3)3.

4. The method according to claim 1 140 Nd- 140 Pr generator separation 140 The method of Pr is characterized in that The complex S1 140 Nd / 140 The preparation process of Pr-DOTP is as follows: first 140 Nd / 140 The Pr solution and the DOTP solution are mixed in a certain amount ratio to obtain a mixed solution, and then the pH value of the mixed solution is adjusted using acid and alkali. 140 Nd / 140 Pr reacts with DOTP to form a complex.

5. The method according to claim 4 140 Nd- 140 Pr generator separation 140 The method of Pr is characterized in that Said 140 Nd / 140 The molar ratio of Pr to DOTP is 1:1-1:1.1; the acid solution is HCl, and the alkali solution is NaOH; the certain pH value is 11±0.5; the reaction temperature of the complex reaction is 80-100°C, and the reaction time is 30-60min.

6. The method according to claim 1 140 Nd- 140 Pr generator separation 140 The method of Pr is characterized in that In S2, the filling material of the anion exchange column includes anion exchange resin and acidic aluminum oxide.

7. The method according to claim 1 140 Nd- 140 Pr generator separation 140 The method of Pr is characterized in that In the S2, the acid includes HCl and HNO3, the concentration of the acid is 0.01-0.1M, and the volume V1 is such that the amount of hydrogen ion substances in the acid is 140 Nd / 140 The amount of the substance of the Pr-DOTP complex is 10 to 100 times; the time t1 is 10 to 30 minutes; and the volume of the pure water is ≥ 2 times the column volume.

8. The method according to claim 1 140 Nd- 140 Pr generator separation 140 The method of Pr is characterized in that In S2 and S3, the conductivity of pure water at 25° C. is less than 5.1 μS / cm.

9. The method according to claim 1 140 Nd- 140 Pr generator separation 140 The method of Pr is characterized in that In S3, the ambient temperature of the anion exchange column is room temperature, and the time t2 is 30 minutes.