Radiolabeled Tamoxifen Analogues for Imaging Breast Cancer with Spect

Abstract

This study is aimed at developing SPECT ligands to image breast tumors. ^99mTc-labeled tamoxifen (TX) analogue was prepared by reacting hydroxyethylthio TX analogue with reduced Tc-IV. The yield was 50–60% (purity >99%). ¹³¹I-TX was prepared by treating tosyl-TX with Na¹³¹I. The yield was 20–25% (>99% purity). Biodistribution studies of both analogues were performed in DMBA-induced mammary tumor-bearing rats (10 μCi/rat, i.v., n=3/timeinterval). Biodistribution ^99mTc-TX at 1, 2, 4, 6 and 18 hrs showed a tumor uptake value (% injected dose/gram tissue) of 0.37±0.058, 0.38±0.066, 0.27±0.041, 0.28±0.124 and 0.10±0.013. Tumor/blood ratio ranged from 0.11 to 0.07. Tumor/muscle ratio ranged from 5.68 to 7.38. Biodistribution of ¹³¹I-TX at 1, 3, 6 and 24 hrs showed a tumor uptake value 0.18±0.062, 0.23±0.152, 0.26±0.166 and 0.27±0.016. When rats primed with estradiol (60 μg/rat, 3 days, s.c), the value changed to 0.30±0.033, 0.42± to 0.039, 0.48±0.107, and 0.40±0.123. Tumor/blood ratio ranged from 1.95 to 11.0. When rats pretreated with DES (1.2 mg/rat, iv), the tumor uptake value changed to 0.32±0.058 (^99mTc-TX, 2 h) and 0.22±0.059 (¹³¹I-TX, 6 h). In rats pretreated with estradiol, a significant increase in tumor uptake value was observed after ¹³¹I-TX postinjection. ^99mTc-TX uptake in tumor could not be blocked by DES, suggesting the uptake was not due to a receptor-mediated process. ¹³¹I-TX may be useful in differentiating functioning ER(+) breast tumors.