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Meeting ReportOncology, Basic Science Track

PET imaging of gonadotropin releasing hormone receptor expression using [18F]-labeled GnRH peptide

Kongzhen Hu
Journal of Nuclear Medicine May 2018, 59 (supplement 1) 1291;
Kongzhen Hu
1Department of Nuclear Medicine Nanfang Hospital, Southern Medical University Guangzhou China
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Abstract

1291

Introduction: PET Imaging of Gonadotropin Releasing Hormone Receptor Expression Using [18F]-Labeled GnRH Peptide Gonadotropin releasing hormone receptor (GnRHR) overexpresses on malignant tumors of human reproductive system, but is not present on most normal tissues. The aim of this study was to develop [18F]-labeled GnRH peptide quantification of GnRHR expression in vivo by PET. Method: The prosthetic group of 4-nitrophenyl-2-18F-fluoropropionate (18F-NFP) was conjugated to the ε-amino group of the D-lysine side chain of [D-Lys6]-GnRH. Cell uptake studies of this tracer 18F-FP-[D-Lys6]-GnRH were performed in GnRHR positive cells of PC3 and GnRHR negative cells of Chinese hamster ovary (CHO). The GnRHR affinity of 19F-FP-[D-Lys6]-GnRH was determined by in vitro competitive binding assay. For in vitro characterization determination of stability, partition coefficients and metabolic stability were carried out. Dynamic microPET and biodistribution studies of 18F-FP-[D-Lys6]-GnRH were evaluated in PC3 human prostate cancer and SKBR3 murine breast tumor models. Results: 18F-FP-[D-Lys6]-GnRH can be produced in 120 min with decay corrected yield of 8 ± 4% (n = 6), radiochemical purity of 96% and specific activity of 20-100 GBq/µmol. In vitro studies showed high GnRHR binding affinity and receptor-specific uptake. The radiotracer was stable in PBS solution and in bovine serum. Dynamic PET imaging demonstrated uptake of tracer in PC3 human prostate tumor model was significant higher than SKBR3 breast tumor models. The Biodistribution data 60 min postinjection confirmed the in vivo receptor-specific tumor accumulation. Conclusion: Our results show that 18F-FP-[D-Lys6]-GnRH can be effective at targeting tumor GnRHR in vivo, with high binding affinity, specificity and metabolic stability. However, due to high activity uptake in kidneys and liver, future studies will improve the pharmacokinetics and further increase tumor uptake.

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Journal of Nuclear Medicine
Vol. 59, Issue supplement 1
May 1, 2018
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PET imaging of gonadotropin releasing hormone receptor expression using [18F]-labeled GnRH peptide
Kongzhen Hu
Journal of Nuclear Medicine May 2018, 59 (supplement 1) 1291;

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PET imaging of gonadotropin releasing hormone receptor expression using [18F]-labeled GnRH peptide
Kongzhen Hu
Journal of Nuclear Medicine May 2018, 59 (supplement 1) 1291;
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