Imaging, biodistribution and therapy potential of Halogenated tamoxifen analogues

Tamoxifen binds to estrogen receptors (ERs) and prevents breast cancer cell proliferation. This study is aimed at developing a ligand for imaging ER (+) breast tumors by positron emission tomography (PET) or single photon emission computed tomography (SPECT). [¹⁸F]-Labeled tamoxifen analogue ([¹⁸F]FTX) was prepared in 30-40% yield and [¹³¹I]-labeled tamoxifen analogue ([¹³¹I]ITX) was prepared in 20-25% yield. In mammary tumor-bearing rats, the biodistribution of [¹⁸F]FTX at 2 h showed a tumor uptake value (% injected dose/gram tissue) of 0.41 ± 0.07; when rats were pretreated with diethylstilbestrol (DES), the value changed to 0.24 ± 0.017. [¹³¹]ITX at 6 h showed a tumor uptake value of 0.26 ± 0.166; when rats were pretreated with DES, the value changed to 0.22 ± 0.044. Priming tumor-bearing rats with estradiol, a tumor uptake value for [¹³¹]ITX was increased to 0.48±0.107 at 6 h. In the [³H]estradiol receptor assay, tumors had a mean estrogen receptor density of 7.5 fmol/mg of protein. In gamma scintigraphic imaging studies with [¹³¹I]ITX, the rabbit uterus uptake can be blocked by pretreatment with DES. Both iodotamoxifen and tamoxifen reduced ER(+) breast tumor growth at the dose of 50 μg in tumor-bearing mice. The findings indicate that tamoxifen analogue uptake in tumors occurs via an ER-mediated process. Both analogues should have potential for diagnosing functioning ER(+) breast cancer.