PET of Follicle-Stimulating Hormone Receptor: Broad Applicability to Cancer Imaging

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• 作者：Hao Hong ; Yongjun Yan ; Sixiang Shi ; Stephen A. Graves ; Lazura K. Krasteva ; Robert J. Nickles ; Min Yang ; Weibo Cai
• 刊名：Molecular Pharmaceutics
• 出版年：2015
• 出版时间：February 2, 2015
• 年：2015
• 卷：12
• 期：2
• 页码：403-410
• 全文大小：407K
• ISSN：1543-8392

文摘

Selective overexpression of follicle-stimulating hormone receptor (FSHR) inside the vascular endothelium of tumors has been confirmed to play critical roles in angiogenesis, tumor invasion, and metastases. The expression level of FSHR correlates strongly with the response of tumors to antiangiogenic therapies. In this study, an immunoPET tracer was developed for imaging of FSHR in different cancer types. A monoclonal antibody (FSHR-mAb) against FSHR was conjugated with S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) and used for subsequent ⁶⁴Cu-labeling. NOTA鈥揊SHR-mAb preserved FSHR specificity/affinity, confirmed by flow cytometry measurements. ⁶⁴Cu-labeling was successfully conducted with decent yields (鈭?5%) and high specific activity (0.93 GBq/mg). The uptake of ⁶⁴Cu-NOTA鈥揊SHR-mAb was 3.6 卤 0.8, 13.2 卤 0.7, and 14.6 卤 0.4 %ID/g in FSHR-positive CAOV-3 tumors at 4, 24, and 48 h postinjection, respectively (n = 3), significantly higher (p < 0.05) than that in FSHR-negative SKOV-3 tumors (2.3 卤 1.2, 8.0 卤 0.9, and 9.1 卤 1.3 %ID/g at 4, 24, and 48 h postinjection, respectively (n = 3)) except at 4 h p.i. FSHR-relevant uptake of ⁶⁴Cu-NOTA鈥揊SHR-mAb was also readily observed in other tumor types (e.g., triple-negative breast tumor MDA-MB-231 or prostate tumor PC-3). Histology studies showed universal FSHR expression in microvasculature of these four tumor types and also prominent expression in tumor cells of CAOV-3, PC-3, and MDA-MB-231. Correlations between tumor FSHR level and uptake of ⁶⁴Cu-NOTA鈥揊SHR-mAb were witnessed in this study. FSHR-specific uptake of ⁶⁴Cu-NOTA-FSHR mAb in different tumors enables its applicability for future cancer theranostic applications and simultaneously establishes FSHR as a promising clinical target for cancer.