Labeling of thymidine with 99mTc-carbonyl and in-vivobiodistribution studies

摘要

Labeled thymidine is used for tumor imaging, since it is incorporated into DNA and thereforeprovides a measure of cell proliferation. For the current study thymidine was functionalized at the C5'position ofthe sugar moiety with the tridentate iminodiacetic acid chelator for complexation and radiolabeling with99mTc(I)-tricarbonyl core. The aim of this study was the labeling of thymidine analogue with 99mTc-tricarbonyltechnique, and the exploration of its potential as radiopharmaceutical in-vivo. Methods: The preparation of the99mTc-precursor consisted in flushing the mixture of sodium carbonate, sodium borohydride and sodiumpotassiumtartrate tetrahydrate with CO gas during 60 min. Pertechnetate was added and the vial was heated for35 min at 75 oC. The reaction was stopped in ice bath, and pH was adjusted to 7. Then 50 μL of the precursorwas added to 10-4 M of the ligand and heated again for 60 min at 75 oC. Radiochemical purity of the precursorand the product was checked by HPLC, TLC and paper chromatography. Biodistribution studies were performedin normal Swiss mice and also in breast-cancer-bearing Sprague-Dawley rats. Results: Yield of the 99mTc(CO)3+was 98.3 ± 0.8%. Radiochemical purity of the [99mTc(CO)3]-thymidine analog was 97.3 ± 0.4%. Biodistributionstudies in normal mice showed the highest uptake by intestine, followed by liver and kidneys. Biodistributionstudies in tumor-bearing rats showed a higher uptake in the kidney than in the liver, probably because theseanimals were anesthetized. Tumor/blood and tumor/muscle ratios were 0.77 and 2.55 respectively. Uptake bythe tumor was 0.18 ± 0.02 %ID/g. Conclusions: Preparation of the 99mTc-precursor and labeling of thymidinewere achieved with very high yield. Uptake by the breast-tumor-bearing rats was low. Other tumor models andlabeling techniques should be used to permit better results.