Methods of Production of Radiopharmaceuticals

1. Iodination techniques, e.g., chloramine T, Bolton and Hunter

2. Tritiation and C-14 reactions

3. Tc-99m reactions by the Stannous Reduction Method result in chelate formation. Most Tc-99m complexes have octahedral structures and are hexa-coordinated. Example:

Sn2+ - 2e- Sn4+

_ TcO4 + 8H+ + 3 e- Tc 4+ + 4H2O

OVERALL,

_ 2Tc7+O4 + 16H+ + 3Sn2+ 2Tc4+ +3Sn4+ +8H2O

4. Tc-99m reactions by the Thiol Reduction Method result in complex formation. In this reaction, two thiol groups (-SH) lose their H-atoms and link together to form a disulfide bridge, comparable to the cystine/cysteine reactions.

5. Biological synthesis, e.g., Co*Cl2 in presence of streptomyces griseus produces Co* vitamin B12; yeast growing in a medium high in Se-75 and low in sulfur produces Se-75 selenomethionine.

Preparation of Radiopharmaceuticals

I. Pertechnetate: used "as is" after elution from the Mo/Tc Generator

II. Tc-99m sulfur colloid

A. To 0.5 ml of 1 N HCl is added Tc-99m pertechnetate and sodium thiosulfate.

B. The mixture is shaken then boiled for 5 min.

C. Acetate buffer is then added and mixture cooled.

D. Ready for quality control and then injection

III. Tc-99m sestamibi and Tc-99m teboroxime

A. Tc-99m pertechnetate is added to a vial of the Sn2+ compound

B. The solution is gently mixed and then boiled for 10 min.

C. Vial is permitted to cool for 10 min

D. Product is ready for quality control and then injection

IV. Other Tc-99m radiopharmaceuticals

A. To vial of freeze-dried cold kit is added a controlled volume of Tc-99m pertechnetate diluted, if necessary, in 0.9% saline solution

B. Solution is shaken gently then permitted to stand for 5 min.

C. Solution is ready for quality control and then injection

IV. Cr-51 RBC

A. 30 ml of patient's blood added to 10 ml ACD solution.

B. 100 µCi of Cr-51 sodium chromate is added to the anticoagulated blood and mixture is incubated for 15 min with occasional gentle agitation.

C. Ascorbic acid is added to terminate the reaction and prevent labeling from continuing in vivo.

D. Labeled cells are ready for reinjection. NOTE: successful labeling of these cells without damaging them requires a 20 ga or larger bore needle.

V. Ready-to-use radiopharmaceuticals

A. Includes all non-technetium products, e.g., Tl chloride, Ga citrate, Xe-133 gas, all iodinated products not prepared on-site; and others.