Journal article
PET of Follicle-Stimulating Hormone Receptor: Broad Applicability to Cancer Imaging
Molecular pharmaceutics, Vol.12(2), pp.403-410
02/02/2015
DOI: 10.1021/mp500766x
PMCID: PMC4351720
PMID: 25581441
Abstract
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 post-injection, 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 post-injection, 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.
Details
- Title: Subtitle
- PET of Follicle-Stimulating Hormone Receptor: Broad Applicability to Cancer Imaging
- Creators
- Hao Hong - University of Wisconsin–MadisonYongjun Yan - University of Wisconsin–MadisonSixiang Shi - University of Wisconsin–MadisonStephen A. Graves - University of Wisconsin–MadisonLazura K. Krasteva - University of Wisconsin–MadisonRobert J. Nickles - University of Wisconsin–MadisonMin Yang - National Health and Family Planning CommissionWeibo Cai - University of Wisconsin Carbone Cancer Center
- Resource Type
- Journal article
- Publication Details
- Molecular pharmaceutics, Vol.12(2), pp.403-410
- DOI
- 10.1021/mp500766x
- PMID
- 25581441
- PMCID
- PMC4351720
- NLM abbreviation
- Mol Pharm
- ISSN
- 1543-8384
- eISSN
- 1543-8392
- Grant note
- DOI: 10.13039/100000054, name: National Cancer Institute, award: 1R01CA169365, P30CA014520; DOI: 10.13039/100000090, name: Congressionally Directed Medical Research Programs, award: W81XWH-11-1-0644; DOI: 10.13039/100000048, name: American Cancer Society, award: 125246-RSG-13-099-01-CCE; DOI: 10.13039/501100001809, name: National Natural Science Foundation of China, award: 81101077, 81171399; DOI: 10.13039/100010495, name: Department of Radiology, University of Wisconsin-Madison, award: 1105-002
- Language
- English
- Date published
- 02/02/2015
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Radiation Oncology
- Record Identifier
- 9984383276102771
Metrics
12 Record Views