PET of follicle-stimulating hormone receptor: Broad applicability to cancer imaging

Hao Hong, Yongjun Yan, Sixiang Shi, Stephen A. Graves, Lazura K. Krasteva, Robert J. Nickles, Min Yang, Weibo Cai

Research output: Journal article publicationJournal articleAcademic researchpeer-review

24 Citations (Scopus)


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-FSHR-mAb preserved FSHR specificity/affinity, confirmed by flow cytometry measurements. 64Cu-labeling was successfully conducted with decent yields (∼25%) and high specific activity (0.93 GBq/mg). The uptake of 64Cu-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 64Cu-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 64Cu-NOTA-FSHR-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.

Original languageEnglish
Pages (from-to)403-410
Number of pages8
JournalMolecular Pharmaceutics
Issue number2
Early online date20 Jan 2015
Publication statusPublished - 2 Feb 2015
Externally publishedYes


  • angiogenesis
  • Cu-64
  • follicle-stimulating hormone receptor (FSHR)
  • immunoPET
  • molecular imaging
  • positron emission tomography (PET)

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery


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