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

PET of follicle-stimulating hormone receptor: broad applicability to cancer imaging.
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DOI:
10.1021/mp500766x
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发表时间:
2015-02-02
影响因子:
4.9
通讯作者:
Cai W
Cai W
中科院分区:
医学2区
文献类型:
--
作者:
Hong H;Yan Y;Shi S;Graves SA;Krasteva LK;Nickles RJ;Yang M;Cai W

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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 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 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.
DOI: 10.1186/1757-2215-6-80
发表时间: 2013-11-20
影响因子: 4
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发表时间: 1997-02-01
期刊: NATURE GENETICS
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影响因子: 3.1
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发表时间: 1998-11-10
影响因子: 11.1
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Dierich, A;Sairam, MR;Sassone-Corsi, P
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