Synthesis of (131)I-labeled-[(131)I]iodo-17-allylamino-17-demethoxy geldanamycin ([(131)I]iodo-17-AAG) and its biodistribution in mice.
OBJECTIVE
The aim of this study was to examine the radioiodinating condition of 17-allylamino-17-demethoxy geldanamycin (17-AAG) and observe its biodistribution in the hepatoma cell line HepA tumorearing ICR mice for understanding the possibility of its application in nuclear medicine.


METHODS
[(131)I]iodo-17-AAG was prepared by the reaction of 17-AAG with Na[(131)I] in the presence of hydrogen peroxide. [(131)I]iodo-17-AAG was purified by high-performance liquid chromatography (HPLC). The stability of [(131)I]iodo-17-AAG was measured by thin-layer chromatography (TLC). The distributions in HepA tumor-bearing ICR mice at 0.5, 1, 4, 8, 24, and 48 hours after injection of [(131)I]iodo-17-AAG were measured. Tumor uptake studies were performed in HepA tumor-bearing ICR mice.


RESULTS
The labeling yield was over 83%. The radiochemical purity of [(131)I]iodo-17-AAG was 99.6% after purification. The specific activity was greater than 4 Ci/micromol. The labeled compound was stable for at least 120 hours in saline at 4 degrees C. It was initially in blood at 5 minutes with 4.79% of injected dose per g of tissue (%ID/g), and then dropped 0.33% ID/g at 24 hours. The uptake in liver, lung, and kidney at 4.44% ID/g, 2.03% ID/g, and 2.17% ID/g decreased with time, and less than 1% ID/g was measured after 24 hours in those organs. There was rapid tumor uptake, which reached 1.26% ID/g at 0.5 hours, the highest uptake at 8 hours. Yet, the [(131)I]iodo-17-AAG in the contralateral muscle was at a low level during the 48 hours. The tumor-contralateral muscle (T/CM) radioactivity ratio for [(131)I]iodo-17-AAG remained constant at all time points.


CONCLUSIONS
[(131)I]iodo-17-AAG can be efficiently radiolabeled at high specific activity, purified by HPLC and stored with little radiolysis at this specific activities. [(131)I]iodo-17-AAG is a promising radiopharmaceutical in nuclear medicine, especially for tumor-targeted radionuclide brachytherapy.
Daozhen
Chen
C
Nuclear Medicine Technology Institution, School of Clinical Medicine, Southeast University, Nanjing, People's Republic of China.
Lu
Liu
L
Min
Yang
Y
Xinyu
Jiang
J
Ying
Huang
H
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D016227:Benzoquinones / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D001918:Brachytherapy / Q000379:methods; D045744:Cell Line, Tumor; D004355:Drug Stability; D054879:Halogenation; D007457:Iodine Radioisotopes / Q000737:chemistry*; D047029:Lactams, Macrocyclic / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D051379:Mice; D008813:Mice, Inbred ICR; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D014018:Tissue Distribution
D000903:Antibiotics, Antineoplastic; D016227:Benzoquinones; D007457:Iodine Radioisotopes; D047029:Lactams, Macrocyclic; C112765:tanespimycin