Evaluation of A Novel GLP-1R Ligand for PET Imaging of Prostate Cancer

Abstract

Glucagon-like peptide 1 receptor (GLP-1R) is an important biomarker for diagnosis and therapy of the endocrine cancers due to overexpression. Recently, in human prostate cancer cell lines the receptor was also observed, therefore it may be a potential target for the disease. 18F-Al-NOTA-MAL-Cys39-exendin-4 holds great promise for GLP-1R. Therefore, the feasibility of the 18F-labeled exendin-4 analog for prostate cancer imaging was investigated; 2) Methods: New probe 18F-Al-NOTA-MAL-Cys39-exendin-4 was made through one-step notation, quality controlled and stability in vitro analyzed. Prostate cancer PC3 cell xenograft model mice were established to primarily evaluated the imaging properties of the tracer via in vivo small animal PET studies. Pathological studies and Western Blots were also performed; 4) Results: PC-3 prostate xenografts were clearly imaged under baseline conditions. At 30 and 60 min postinjection, the tumor uptakes were 2.90±0.41%ID/g and 2.26±0.32 %ID/g respectively. The presence of cys39-exendin-4 significantly reduced the tumor uptake to 0.82±0.10 %ID/g at 60 min p.i. Findings of ex vivo biodistribution studies were similar to those of in vivo PET imaging. The tumors to blood and muscles were improved significantly with the increase of time due to rapid clearance of the tracer from normal organs. Blockings were displayed in the GLP-1R positive tumor and normal organs after coinjection of excessive unlabeled peptides with the tracer. Immunohistochemistry and Western Blots results confirmed that GLP-1R was widely expressed in PC-3 prostate xenografts and PC-3 cells; 5) Conclusions: 18F-Al labeled exendin-4 analog might be a promising tracer for in vivo detecting GLP-1R positive prostate cancer with the advantage of facile synthesis and favorable pharmacokinetics. It may be useful in differential diagnosis, molecularly targeted therapy and prognosis of the cancers.

Preliminary evaluation of GLP-1R PET in the diagnosis and risk stratification of pheochromocytomas

“…This labeling process took only 30 min and the final product did not require further purification. We then validated the characteristics of 18 F-Al-NOTA-MAL-Cys 39 -exendin-4 such as high specificity and low abdominal uptake, and demonstrated its reliable diagnostic performance in diabetes, insulinoma and prostate cancer [21][22][23]. In this present study, we intend to develop another novel radiotracer using positron nuclide 68 Ga.…”

Analysis of the Prognosis Related Genes in HER2+ Breast Cancer Based on Weighted Gene Co-expression Network Analysis

“…GLP1R (Glucagon Like Peptide 1 Receptor) is a Protein Coding gene which is a member of G protein coupled receptor family. GLP-1R is an important target when treating of type 2 diabetes and obesity [32][33][34]. Recent studies have shown that GLP-1R activation has a cytoreductive effect on human pancreatic cancer cells [35].…”