Method for preparing a suspension of radioactive yttrium phosphate particles

Abstract

A method for preparing a radioactive yttrium salt particle suspension comprising multiple steps, including using a hydrothermal process in which a solution of soluble yttrium salts from the group of yttrium chloride, yttrium nitrate, yttrium sulfate, and yttrium bromide is mixed with a stoichiometric excess of phosphate and a solution of sodium phosphate, which when mixed have a suitable pH.

Description

Disclosed Content

[0001] 〔Field and Background of the Invention〕 A method for preparing a radioactive yttrium phosphate particle suspension for the treatment of tumors including solid tumors.

[0002] As referred to herein Any Patents and Publications is , incorporated by reference this specification into .

[0003] 〔Summary of the Invention〕 The claimed method is the preparation of radioactive yttrium phosphate particles of a size preferred for interstitial application in solid tumors.

[0004] The above and other features and advantages of the present invention will be more readily appreciated as they become better understood by reference to the following detailed description of the preferred embodiments of the present invention when interpreted in conjunction with the accompanying drawings.

Brief Description of the Drawings

[0005]

Figure 1

Figure 2

[0006] The foregoing description of specific embodiments of the present invention has been presented for purposes of illustration and description. They are not intended to be exhaustive or to limit the invention to the precise form disclosed, and many modifications and variations are possible in light of the above teachings and drawings. The exemplary embodiments were chosen and described in order to best explain the principles of the invention and its practical application to enable those skilled in the art and manufacturers of products to make various modifications suitable for the particular intended uses and to best utilize the invention and its various embodiments.

[0007] [Detailed Description of the Invention] A method for preparing a suspension of radioactive yttrium salt particles, comprising using a hot water process in which a solution of a soluble yttrium salt from the group of yttrium chloride, yttrium nitrate, yttrium sulfate and yttrium bromide is mixed with a solution of sodium phosphate having a pH in the range of 1.5 to 8 when mixed with a stoichiometric excess of phosphate. preferably a pH in the range of 7 - 8 These solutions are mixed while continuously stirring, rapidly heated to 150 °C in a sealed container, held for 1 to 10 hours to cause a conversion of more than 99.99% of the soluble yttrium to insoluble YPO4, achieving the desired particle size distribution, and;

[0008] resulting in the desired particle size distribution of YPO4 particles suspended in buffered physiological saline at a neutral pH suitable for direct injection into human or animal tissue.

[0009] A radioactive particle suspension having a particle size of less than 2 μm.

[0010] A radioactive particle suspension composed of at least 90% of the total particle volume consisting of particles in the range of 0.1 μm to 2 μm.

[0011] The method further includes that the initial concentration of soluble yttrium in the mixed solution is in the range of 0.5 to 3.0 mol / liter, and the stoichiometric excess of phosphate is in the range of 10 to 100%.

[0012] The method further includes that the initial concentration of soluble yttrium in the mixed solution is in the range of 0.5 to 3.0 mol / liter, and the stoichiometric excess of phosphate is in the range of 10 to 100%.

[0013] The method further includes that the initial concentration of soluble yttrium in the mixed solution is 0.08 mol / L and the stoichiometrically excessive phosphate is 25%.

[0014] This method includes preparing a particle precursor solution, mixing and heating it to form YPO4 particles by controlled precipitation, and then post-treating the particles to achieve a suspension of YPO4 particles in an aqueous phosphate-buffered saline solution at a neutral pH suitable for injection into human or animal tissues, further including a particle suspension formed thereby.

[0015] This method further includes a particle suspension, wherein the post-treatment consists of rinsing the particles three times with a sterile phosphate-buffered saline (PBS) solution and removing or adding PBS to achieve the final desired volume.

[0016] This method further includes a particle suspension, wherein the post-treatment consists of adjusting the pH of the final solution with sodium hydroxide and then removing the excess solution or adding sterile PBS to achieve the final desired volume.

[0017] This method further includes making the particles radioactive by adding a small amount of soluble radioisotope to the particle precursor solution such that it becomes uniformly incorporated into the insoluble yttrium phosphate particle matrix, a particle suspension in which the yttrium phosphate particles serve as a source of distributed therapeutic radiation for treating cancerous tumors and other diseases.

[0018] This method further includes a yttrium phosphate particle suspension, which, after being mixed with a biocompatible hydrogel or other suitable liquid carrier solution in a 1:4 volume ratio for injection into human or animal tissues, has a particle concentration in the range of 40 mg / mL to 125 mg / mL to facilitate imaging by X-ray computed tomography. 〔Example I〕 One exemplary process for practicing the method of the present invention is shown below: Step 1 - Prepare the reagents, Step 1.1 - Weigh out a non-radioactive (i.e., Y-89) yttrium salt from the group of yttrium chloride, yttrium nitrate, yttrium sulfate, and yttrium bromide, quantitatively transfer it to a volumetric flask; add deionized water; stir to mix completely, Step 1.2 - 89 Y +3 Draw the solution from the volumetric flask into a syringe, push the solution through a filter, and collect the solution in a sterile container, Step 1.3 - Prepare and filter 0.15M Na 2 HPO4 reagent and 0.05M HCl reagent; store the reagents at room temperature, by preparing, 90 YCl 3 Step 2 - Prepare a radioactive 90 YCl 3 solution by adding a sufficient volume of 0.05M HCl to the source vial containing to achieve the recovery of the desired amount of radioactive material from the source vial, by 89 Y+ 90 preparing, 4 Step 3 - Perform a radioactive ( Y)PO 2 synthesis procedure, Step 3.1 - Add H 2 O to the microwave reaction vial using a sterile magnetic stir bar; place the reaction vessel on a stirring plate; stir continuously, 4 Step 3.2 - Add 0.15M Na HPO 89 Y +3 Step 3.3 - Add the solution, Step 3.4 - Add 90 Y from the source vial into 0.05M HCl, Step 3.5 - Record the final pH, Step 3.6 - Transfer the vial to a microwave reactor, Step 3.7 - Set the reaction temperature to a temperature in the range of 110°C - 160°C and the reaction time to 1 hour - 20 hours, and start the reactor, by performing, Step 4 - Perform the final step, which is Step 4.1 - Place the microwave vial with the particles in a centrifuge and centrifuge the particles, Step 4.2 - Remove the supernatant and replace it with sterile phosphate-buffered saline, and repeat steps 4.1 and 4.2 two more times, Step 4.3 - Remove the excess supernatant from the vial, Step 4.4 - Appropriately label the vial To include and implement [Example II] Starting from the method of Example I, the following modifications and additions are made to the steps described in Example I: Step 1.1 - 1.0M 89YCl 3 , non-radioactive (i.e., Y-89) YCl 3 ·6H 2 Weigh out YCl₃O, quantitatively transfer it to a volumetric flask; add deionized water to the volumetric flask; stir to mix thoroughly. Step 1.2 - Draw up 1.0M 89 YCl 3 solution into a syringe, push the solution through a filter, and collect the solution in a sterile container. Step 3 - Radioactive ( 90 Y+ 89 Y)PO 4 synthesis procedure Step 3.1 - Add 1.0 mL of H₂O to a microwave reaction vial using a sterile magnetic stir bar, place the reaction vessel on a stirring plate, and stir continuously. 2 Step 3.2 - Add 2.67 mL of 0.15M Na₂HPO₄. Step 3.3 - Add 0.32 mL of 2 YCl 4 solution. Step 3.4 - Add up to 0.05 mL of 89 YCl 3 solution from the source vial into 0.05M HCl. Step 3.5 - Record the final pH. 90 Step 3.6 - Transfer the vial to a microwave reactor. Step 3.7 - Set the reaction temperature to 150 °C, set the reaction time to 1 hour, and start the reactor. Step 4 - Final step Step 4.1 - Adjust the pH of the product solution to a pH range of 1.5 - 8 with 1.0N NaOH. Step 4.3 - Remove the supernatant, leaving 1.0 mL in the vial for each planned tumor treatment. [Example III] Starting from the method of Example II, the following modifications and additions are made to the steps described in Example II: Step 1.1 - 1.0M YCl : non-radioactive (i.e., Y-89) YCl 89 Weigh out YCl₃O in approximately 0.01 g units (for one planned tumor treatment) in an amount of 3.03 ± 0.15 g, quantitatively transfer it to a 10 mL volumetric flask; add deionized water to the 10 mL mark; stir to mix thoroughly. 3 Step 1.2 - Draw up ~8 - 10 mL of 1.0M 3 6H 2 YCl solution into a syringe, push the solution through a filter, and collect the solution in a sterile container. 89 Step 1.3 - Prepare and filter 0.15M Na₂HPO₄ reagent and 0.05M HCl reagent. 3 Step 4 - Final step Step 4.1 - Adjust the pH of the product solution to a pH range of 7 - 8 with 1.0N NaOH. 2 ​ 4 ​ ​ ​ Step 4.2 - Remove the supernatant leaving 1.0 mL in the vial for each of the scheduled tumor treatments. [Example IV] An alternative method for preparing a radioactive yttrium phosphate particle suspension is a hot water process in which a solution of a yttrium salt from the group of yttrium chloride, yttrium nitrate, yttrium sulfate and yttrium bromide is mixed with a solution of sodium phosphate that is stoichiometrically in excess and has a pH in the range of 1.5 to 8 when mixed, mixing the solutions while continuously stirring, heating to a range of 110 °C to 160 °C in a sealed container and holding for 1 to 20 hours to effect a conversion of more than 99.99% of the soluble yttrium to insoluble YPO 4 to achieve a particle size distribution where the particles are 2 μm or less, suspending the YPO 4 particles in buffered physiological saline at neutral pH suitable for direct injection into human or animal tissue to produce the desired particle size distribution of the particles, and including. [Example V] Starting from the method of Example IV, the following modifications and additions are made to the steps described in Example IV: The heating of the mixed solution is rapid heating. [Example VI] Starting from the method of Example V, the following modifications and additions are made to the steps described in Example V: The radioactive particle suspension used by this method contains at least 90% of the total particle volume consisting of particles in the range of 0.1 μm to 2 μm. [Example VII] Starting from the method of Example VI, the following modifications and additions are made to the steps described in Example VI: Use an initial concentration of soluble yttrium in the mixed solution that is in the range of 0.5 to 3.0 moles / liter and the stoichiometrically excess phosphate is in the range of 10 to 100%. [Example VIII] Starting from the method of Example VI, the following modifications and additions are made to the steps described in Example VI: Use an initial concentration of soluble yttrium in the mixed solution that is 0.08 moles / liter and the stoichiometrically excess phosphate is 25%. [Example IX] Starting from the method of Example IV, the following modifications and additions are made to the steps described in Example IV: Mixing and heating the particle suspension formed by preparing a particle precursor solution to form YPO 4 particles by controlled precipitation, and then post-treating the particles to achieve a suspension of YPO 4 particles in phosphate buffered saline aqueous solution at neutral pH suitable for injection into human or animal tissue. [Example X] Start with the method of Example IX and make the following modifications and additions to the steps described in Example IX: Perform post-treatment by rinsing the particles three times with sterile phosphate-buffered saline (PBS) solution and removing or adding PBS to achieve the final desired volume. [Example XI] Start with the method of Example IX and make the following modifications and additions to the steps described in Example IX: Perform post-treatment by adjusting the pH of the final solution with sodium hydroxide and then removing the excess solution or adding sterile PBS to achieve the final desired volume. [Example XII] Start with the method of Example IV and make the following modifications and additions to the steps described in Example IV: Use a particle suspension in which the yttrium phosphate particles are radioactive so as to serve as a distribution source of therapeutic radiation for treating cancerous tumors and other diseases. Make the particles radioactive by adding a small amount of soluble radioisotope to the particle precursor solution of Example IV such that it becomes uniformly incorporated into the insoluble yttrium. [Example XIII] Start with the method of Example IV and make the following modifications and additions to the steps described in Example IV: Use the yttrium phosphate particle suspension of Example IV in which the particle concentration is in the range of 40 mg / mL to 125 mg / mL to facilitate imaging by X-ray computed tomography after mixing with a biocompatible hydrogel or other suitable liquid carrier solution in a volume ratio of 1 to 4 for injection into human or animal tissue. Use a solution of sodium phosphate having a stoichiometric excess of phosphate and a pH in the range of 7 to 8.

[0019] 〔Embodiment〕 (1) A method for preparing yttrium phosphate particles, comprising: Step 1 - Preparing the reagents, which involves Step 1.1 - Weighing a non-radioactive (i.e., Y-89) yttrium salt from the group of yttrium chloride, yttrium nitrate, yttrium sulfate, and yttrium bromide, quantitatively transferring it to a volumetric flask; adding deionized water; stirring to mix thoroughly, Step 1.2 - 89 Y +3 Drawing the solution from the volumetric flask into a syringe, pushing the solution through a filter, and collecting the solution in a sterile container, Step 1.3 - Preparing and filtering 0.15M Na2HPO4 reagent and 0.05M HCl reagent; storing the reagents at room temperature, Step 2 - Preparing a radioactive 90 YCl3 solution, which involves 90 Adding a sufficient volume of 0.05M HCl to the source vial containing YCl3 to achieve the recovery of a desired amount of radioactive material from the source vial, Step 3 - The radioactive ( 90 Y+ 89 Y)PO4 synthesis procedure, which involves Step 3.1 - Adding H2O to a microwave reaction vial using a sterile magnetic stir bar; placing the reaction vessel on a stirring plate; continuously stirring, Step 3.2 - Adding 0.15M Na2HPO4, Step 3.3 - 89 Y +3 Adding the solution, Step 3.4 - Adding 90 Y from the source vial into 0.05M HCl, Step 3.5 - Recording the final pH, Step 3.6 - Transferring the vial to a microwave reactor, Step 3.7 - Setting the reaction temperature to a temperature in the range of 110°C to 160°C and setting the reaction time to 1 hour to 20 hours, and starting the reactor, the synthesis procedure, Step 4 - The final step, which involves Step 4.1 - Place the microwave vial together with the particles in a centrifuge, subject the particles to centrifugation, Step 4.2 - Remove the supernatant and replace it with sterile phosphate buffered saline, and repeat steps 4.1 and 4.2 two more times, Step 4.3 - Remove the excess supernatant from the vial, Step 4.4 - As a final step, label the vial with the identity, lot number, and date of manufacture, A method comprising. (2) Step 1.1 - Weigh 1.0 M 89 YCl3: non-radioactive (i.e., Y-89) YCl3·6H2O, quantitatively transfer it to a volumetric flask; add deionized water to the volumetric flask; stir to mix thoroughly, Step 1.2 - Draw up the 1.0 M 89 YCl3 solution into a syringe, push the solution through a filter, and collect the solution in a sterile container, Step 3 - Radioactive ( 90 Y+ 89 Y)PO4 synthesis procedure, Step 3.1 - Add 1.0 mL of H2O to a microwave reaction vial using a sterile magnetic stir bar; place the reaction vessel on a stirring plate; stir continuously, Step 3.2 - Add 2.67 mL of 0.15 M Na2HPO4, Step 3.3 - Add 0.32 mL of 89 YCl3 solution, Step 3.4 - Add up to 0.05 mL of 90 Y in 0.05 M HCl from the source vial, Step 3.5 - Record the final pH, Step 3.6 - Transfer the vial to a microwave reactor, Step 3.7 - Set the reaction temperature to 150 °C and the reaction time to 1 hour, and start the reactor, the synthesis procedure, Step 4 - As the final step, Step 4.1 - Adjust the pH of the product solution to a pH range of less than 1.5 to 8 with 1.0 N NaOH, Step 4.3 - The final step of removing the supernatant, leaving 01.0 mL in the vial for each planned tumor treatment, A method for preparing yttrium phosphate particles according to Embodiment 1, further comprising. (3) Step 1.1 - 1.0 M 89 YCl3: Weigh out non-radioactive (i.e., Y-89) YCl3·6H2O in an amount of 3.03 ± 0.15 g in units of approximately 0.01 g for one planned tumor treatment, quantitatively transfer it to a 10 mL volumetric flask; add 10 mL of deionized water to the 10 mL mark; stir to mix thoroughly, Step 1.2 - Draw up ~8 - 10 mL of 1.0 M 89 YCl3 into a syringe, push the solution through a filter, and collect the solution in a sterile container, Step 1.3 - Prepare and filter 0.15 M Na2HPO4 reagent and 0.05 M HCl reagent, Step 3 - Radioactive ( 90 Y+ 89 Y)PO4 synthesis procedure, Step 4 - The final step, Step 4.1 - Adjust the pH of the product solution to a pH range of 7 - 8 with 1.0 N NaOH, Step 4.3 - The final step of removing the supernatant, leaving 1.0 mL in the vial for each planned tumor treatment, A method for preparing a certain volume of yttrium phosphate particles according to Embodiment 2, further comprising. (4) A method for preparing a radioactive yttrium phosphate particle suspension, A solution of a yttrium salt from the group of yttrium chloride, yttrium nitrate, yttrium sulfate, and yttrium bromide is mixed with a solution of sodium phosphate having a stoichiometric excess of phosphate and having a pH in the range of 1.5 - 7.4, preferably in the range of 7 - 8 when mixed, using a hot water process, Mix the solutions while continuously stirring, rapidly heat to a range of 110 °C to 160 °C in a sealed container, hold for 1 to 20 hours to cause a conversion of more than 99.99% of soluble yttrium to insoluble YPO4, and achieve a desired particle size distribution, result in a desired particle size distribution of YPO4 particles suspended in buffered physiological saline at neutral pH suitable for direct injection into human or animal tissue, A method comprising: (5) The method according to embodiment 4, further comprising the radioactive particle suspension, wherein the particle size is less than 2 μm.

[0020] (6) The method according to embodiment 5, further comprising the radioactive particle suspension, which is composed of at least 90% of the total particle volume of particles in the range of 0.1 μm to 2 μm. (7) The method according to embodiment 6, further comprising that the initial concentration of soluble yttrium in the mixed solution is in the range of 0.5 to 3.0 mol / liter, and the stoichiometrically excessive phosphate is in the range of 10 to 100%. (8) The method according to embodiment 6, further comprising that the initial concentration of soluble yttrium in the mixed solution is 0.08 mol / liter, and the stoichiometrically excessive phosphate is 25%. (9) The method according to embodiment 4, further comprising the particle suspension formed by preparing the particle precursor solution of embodiment 4, mixing and heating to form the YPO4 particles by controlled precipitation, and then post-treating the particles to achieve a suspension of YPO4 particles in an aqueous phosphate buffered saline solution at neutral pH suitable for injection into human or animal tissue. (10) The method according to embodiment 9, further comprising the particle suspension, wherein the post-treatment consists of rinsing the particles three times with a sterile phosphate buffered saline (PBS) solution and removing or adding PBS to achieve the final desired volume.

[0021] (11) The method according to embodiment 9, further comprising the particle suspension, wherein the post-treatment consists of adjusting the pH of the final solution with sodium hydroxide and then removing the excess solution or adding sterile PBS to achieve the final desired volume. (12) The particle suspension of embodiment 4, wherein the yttrium phosphate particles are radioactive so as to serve as a source of distribution of therapeutic radiation for treating cancerous tumors and other diseases, and radioactivating the particles by adding a small amount of soluble radioisotope to the particle precursor solution of embodiment 4 such that it becomes uniformly incorporated into the insoluble yttrium phosphate particle matrix. The method according to embodiment 4, further comprising the above. (13) The method according to embodiment 4, further comprising the yttrium phosphate particle suspension of embodiment 4, wherein after mixing with a biocompatible hydrogel or other suitable liquid carrier solution in a volume ratio of 1:4 for injection into human or animal tissue, the particle concentration is in the range of 40 mg / mL to 125 mg / mL to facilitate imaging by X-ray computed tomography.

Claims

1. A method for preparing a suspension of radioactive yttrium phosphate particles, comprising: mixing a radioactive solution of a yttrium salt from the group consisting of yttrium chloride, yttrium nitrate, yttrium sulfate, and yttrium bromide with a solution of sodium phosphate having a pH in the range of 1.5 to 8 when mixed with a stoichiometrically excess phosphate, using a hot water process; Mix the solution while continuously stirring, heat it in a sealed container to a range of 110°C to 160°C, and hold for 1 to 20 hours to cause more than 99.99% conversion to insoluble YPO of soluble yttrium ４ result in a conversion exceeding 99.99% to achieve a particle size distribution with particles 2 μm or less in size, and YPO suspended in buffered saline at neutral pH suitable for direct injection into human or animal tissue ４ resulting in the desired particle size distribution of the particles, and a method comprising: Weigh out a non-radioactive (i.e., Y-89) yttrium salt from the group of yttrium chloride, yttrium nitrate, yttrium sulfate, and yttrium bromide, quantitatively transfer it to a volumetric flask; add deionized water; and stir to mix thoroughly to ８９ Y ３＋ prepare a solution, and The aforesaid ８９ Y ３＋ solution is drawn up from the volumetric flask into the syringe, and the ８９ Y ３＋ solution is pushed through the filter, and the ８９ Y ３＋ solution is collected in a sterilized container, 0.15 M Na ２ HPO ４ Prepare and filter the reagent and 0.05 M HCl reagent, and store the reagent at room temperature, and Radioactivity ９０ YCl ３ preparing a solution by ９０ YCl ３ adding a sufficient volume of the 0.05 M HCl reagent to a source vial containing the YCl to achieve recovery of a desired amount of radioactive material from the source vial Radioactivity ( ９０ Y+ ８９ Y)PO ４ is to carry out a synthesis procedure, wherein the synthesis procedure is Add H ２ O to the microwave reaction vial using a sterilized magnetic stir bar and place the microwave reaction vial on a stirring plate; continuously stir and add the 0.15 M Na ２ HPO ４ reagent, the dissolved radioactive ９０ YCl ３ solution from the source vial, and the ８９ Y ３＋ solution, and transfer the microwave reaction vial to a microwave reactor setting the reaction temperature to a temperature in the range of 110°C to 160°C, setting the reaction time to 1 hour to 20 hours, and starting the microwave reactor; placing the microwave reaction vial together with the particles in a centrifuge and performing a final step of centrifuging the particles; removing the supernatant, replacing it with sterile phosphate buffered saline, and repeating the final step two more times; removing excess supernatant from the microwave reaction vial; further comprising:

2. The neutral pH is 7 to 8, and the YPO ４ The method according to claim 1, wherein the particle median diameter of the particles is 0.2450 μm or less.

3. The neutral pH is 7.35 to 7.4, and the YPO ４ Since the particle median diameter of the particles is 0.1844 μm to 0.2450 μm, the YPO ４ The method according to claim 2, wherein the particles provide interstitial effectiveness for cell space application.

4. The aforesaid ８９ Y ３＋ solution is a 1.0 M ８９ YCl ３ solution, and the reaction being carried out at a temperature of 150°C for 1 hour; the pH of the product solution being adjusted to a pH range of 1.5 to 8 with 1.0 N NaOH; removing the supernatant and leaving 1.0 mL in the microwave reaction vial for each planned tumor treatment, the method according to claim 1.

5. The non-radioactive 1.0 M ８９ YCl ３ solution is prepared for a single tumor treatment by adding 10 mL of deionized water to 3.03 ± 0.15 g ８９ YCl ３ 6H ２ O up to the 10 mL mark in a 10 mL volumetric flask and stirring to mix thoroughly, and the pH of the product solution is adjusted to a pH range of 7 to 8 with 1.0 N NaOH, the method according to claim 4.

6. the heating in the sealed container being rapid heating of the mixed solution, the method according to claim 1.

7. the resulting suspension of radioactive yttrium phosphate particles being composed of at least 90% of the total particle volume containing particles in the range of 0.1 μm to 2 μm, the method according to claim 6.

8. the initial concentration of the soluble yttrium in the mixed solution being in the range of 0.05 to 3.0 mol / L and the stoichiometrically excess phosphate being in the range of 10 to 100%, the method according to claim 7.

9. the initial concentration of the soluble yttrium in the mixed solution being 0.08 mol / L and the stoichiometrically excess phosphate being 25%, the method according to claim 8.

10. After mixing with a biocompatible hydrogel or other suitable liquid carrier solution in a volume ratio of about 1 to 4 for injection into human or animal tissue, the particle concentration of the suspension of radioactive yttrium phosphate particles is in the range of 40 mg / mL to 125 mg / mL to facilitate imaging by X-ray computed tomography. The method according to claim 1, wherein the sodium phosphate solution has a stoichiometric excess of phosphate and a pH in the range of 7 to 8. **Claim 11**: A method for preparing a suspension of radioactive yttrium phosphate particles, wherein a radioactive solution of a yttrium salt from the group consisting of yttrium chloride, yttrium nitrate, yttrium sulfate and yttrium bromide is mixed with a solution of sodium phosphate having a stoichiometric excess of phosphate and a pH in the range of 1.5 to 8 when mixed, using a hydrothermal process; mixing the solutions while stirring continuously, heating to a range of 110 °C to 160 °C in a sealed container and holding for 1 to 20 hours to cause a conversion of more than 99.99% of soluble yttrium to insoluble YPO₄, achieving a particle size distribution with particles being 2 μm or less; producing a desired particle size distribution of YPO₄ particles suspended in buffered physiological saline at neutral pH suitable for direct injection into human or animal tissue; comprising: weighing out a non-radioactive (i.e., Y-89) yttrium salt from the group consisting of yttrium chloride, yttrium nitrate, yttrium sulfate and yttrium bromide, quantitatively transferring it to a volumetric flask; adding deionized water; and preparing an ⁸⁹Y³⁺ solution by stirring to mix completely; drawing the ⁸⁹Y³⁺ solution from the volumetric flask into a syringe, forcing the ⁸⁹Y³⁺ solution through a filter, and collecting the ⁸⁹Y³⁺ solution in a sterile container; preparing and filtering 0.15 M Na₂HPO₄ reagent and 0.05 M HCl reagent, and storing the reagents at room temperature; preparing a radioactive ⁹⁰YCl₃ solution by adding a sufficient volume of the 0.05 M HCl reagent to a source vial containing ⁹⁰YCl₃ to achieve the recovery of a desired amount of radioactive material from the source vial; performing a synthesis procedure for radioactive (⁹⁰Y + ⁸⁹Y)PO₄, wherein the synthesis procedure is Add H₂O to the reaction vial using a sterilized magnetic stir bar, and place the reaction vial on a stirring plate; continuously stir and add the 0.15 M Na₂HPO₄ reagent, the dissolved radioactive 90YCl₃ solution from the source vial, and the 89Y³⁺ solution, and transfer the reaction vial to a reactor. Set the reaction temperature to a temperature in the range of 110 °C to 160 °C, set the reaction time to 1 hour to 20 hours, and start the reactor. Put the reaction vial together with the particles into a centrifuge and perform the final step of centrifuging the particles. Remove the supernatant, replace it with sterilized phosphate-buffered saline, and repeat the final step two more times. Remove the excess supernatant from the reaction vial. A method further comprising.

12. The method according to claim 11, wherein the neutral pH is 7 to 8 and the particle median diameter of the YPO₄ particles is 0.2450 μm or less.

13. The method according to claim 12, wherein the neutral pH is 7.35 to 7.4 and the particle median diameter of the YPO₄ particles is 0.1844 μm to 0.2450 μm, whereby the YPO₄ particles provide interstitial effectiveness for cell space applications.

14. The 89Y³⁺ solution is a 1.0 M 89YCl₃ solution. The reaction is carried out at a temperature of 150 °C for 1 hour. The pH of the product solution is adjusted to a pH range of 1.5 to 8 with 1.0 N NaOH. The supernatant is removed and 1.0 mL is left in the reaction vial for each planned tumor treatment. The method according to claim 11.

15. The non-radioactive 1.0 M 89YCl₃ solution is prepared for one planned tumor treatment by adding 10 mL of deionized water to 3.03 ± 0.15 g of 89YCl₃·6H₂O in a 10 mL volumetric flask up to the 10 mL mark and stirring to mix completely, and the pH of the product solution is adjusted to a pH range of 7 to 8 with 1.0 N NaOH. The method according to claim 14.

16. The method according to claim 11, wherein the heating in the sealed container is rapid heating of the mixed solution.

17. The method according to claim 16, wherein the generated suspension of radioactive yttrium phosphate particles is composed of at least 90% of the total particle volume containing particles in the range of 0.1 μm to 2 μm.

18. The method according to claim 17, wherein the initial concentration of the soluble yttrium in the mixed solution is in the range of 0.05 to 3.0 mol / liter, and the stoichiometrically excessive phosphate is in the range of 10 to 100%.

19. The method according to claim 18, wherein the initial concentration of the soluble yttrium in the mixed solution is 0.08 mol / liter, and the stoichiometrically excessive phosphate is 25%.

20. After being mixed in a volume ratio of about 1 to 4 with a biocompatible hydrogel or other suitable liquid carrier solution for injection into human or animal tissue, the particle concentration of the suspension of radioactive yttrium phosphate particles is in the range of 40 mg / mL to 125 mg / mL so as to facilitate imaging by X-ray computed tomography, The method according to claim 11, wherein the solution of sodium phosphate has the stoichiometrically excessive phosphate and a pH in the range of 7 to 8.

Images