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 (64)Cu-labeling.
NOTA-FSHR-mAb preserved FSHR specificity/affinity, confirmed by flow cytometry measurements. (64)Cu-labeling was successfully conducted with decent yields (∼25%) and high specific activity (0.93 GBq/mg). The uptake of (64)Cu-NOTA-FSHR-mAb was 3.6 ± 0.8, 13.2 ± 0.7, and 14.6 ± 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 ± 1.2, 8.0 ± 0.9, and 9.1 ± 1.3 %ID/g at 4, 24, and 48 h postinjection, respectively (n = 3)) except at 4 h p.i. FSHR-relevant uptake of (64)Cu-NOTA-FSHR-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 (64)Cu-NOTA-FSHR-mAb were witnessed in this study. FSHR-specific uptake of (64)Cu-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.