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Imaging, biodistribution and therapy potential of halogenated tamoxifen analogues
1Division of Diagnostic Imaging, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Abstract:
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. [131I]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 [131I]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 iodo-tamoxifen and tamoxifen reduced ER(+) breast tumor growth at the dose of 50 micrograms 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.
Insights
Researchers developed radiolabeled tamoxifen analogues for imaging estrogen receptor-positive breast tumors. These compounds show potential for diagnosing ER(+) breast cancer via nuclear imaging techniques.
Area of Science:
- Nuclear medicine
- Oncology
- Radiochemistry
Background:
- Tamoxifen is an estrogen receptor (ER) antagonist used in breast cancer treatment.
- Accurate imaging of ER-positive (ER(+)) breast tumors is crucial for diagnosis and treatment monitoring.
- Developing specific imaging ligands for ER(+) tumors can enhance diagnostic capabilities.
Purpose of the Study:
- To develop novel radiolabeled tamoxifen analogues for imaging ER(+) breast tumors using PET or SPECT.
- To evaluate the tumor uptake and specificity of these analogues in preclinical models.
Main Methods:
- Synthesis of [18F]-labeled tamoxifen analogue ([18F]FTX) and [131I]-labeled tamoxifen analogue ([131I]ITX).
- Biodistribution studies in mammary tumor-bearing rats and rabbits.
- Estrogen receptor binding assays and gamma scintigraphic imaging.
- Evaluation of tumor growth inhibition in mice.
Main Results:
- [18F]FTX and [131I]ITX were prepared with acceptable yields.
- [18F]FTX showed significant tumor uptake in rats, which was reduced by diethylstilbestrol (DES) pretreatment.
- [131I]ITX also demonstrated tumor uptake, which was enhanced by estradiol priming and blocked by DES in rabbits.
- Tumors exhibited high estrogen receptor density, and both analogues reduced ER(+) breast tumor growth.
Conclusions:
- Tamoxifen analogue uptake in tumors is mediated by estrogen receptors.
- The developed radiolabeled tamoxifen analogues show promise for diagnosing functioning ER(+) breast cancer.
- These ligands could be valuable tools for nuclear imaging of ER(+) breast tumors.