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Neoplasma Vol.67, No.1, p.27-36, 2020 |
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Title: Preliminary evaluation of GLP-1R PET in the diagnosis and risk stratification of pheochromocytomas | ||
Author: M. LI, Y. LIU, Y. XU, Y. LI, D. PAN, L. WANG, J. YAN, X. WANG, R. YANG, M. YANG | ||
Abstract: Noninvasive imaging methods for the diagnosis and risk stratification of pheochromocytomas (PHEOs) remain a great clinical challenge. The glucagon-like peptide-1 receptor (GLP-1R) has been validated to be overexpressed in PHEOs and therefore may be a reliable target for PHEOs. In this study, we firstly synthesized a novel radiotracer 68Ga-NOTA-MAL-Cys39-exendin-4 that specifically targets GLP-1R and evaluated the performance of GLP-1R PET for the diagnosis and risk stratification of PHEOs. Cys39-exendin-4 was conjugated to NOTA-MAL and then radiolabeled with 68Ga. The reaction was completed within 20 min with a yield of 91.6±2.8%. In vitro cell uptake studies validated its high specificity. PET images showed promising tumor visualization with high uptake (1.88±0.10 %ID/g for PC-12 poorly differentiated tumors and 1.09±0.003 %ID/g for PC-12 highly differentiated tumors at 30 min after injection). There was a significant difference in the uptake of 68Ga-NOTA-MAL-Cys39-exendin-4 between PC-12 poorly and highly differentiated tumors (p<0.001), but no significant difference could be observed by 18F-FDG PET. Biodistribution results confirmed the findings of GLP-1R PET and demonstrated that 131I-MIBG couldn’t be used for the risk stratification of PHEOs. Immunohistochemistry (IHC) staining revealed differences in GLP-1R expression between PC-12 poorly and highly differentiated tumor tissues. These results demonstrated that 68Ga-NOTA-MAL-Cys39-exendin-4 could specifically target GLP-1R with favorable pharmacokinetic properties. GLP-1R PET can be used for PHEOs detection and has potential for the risk stratification of PHEOs. |
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Keywords: Glucagon-like peptide-1 receptor (GLP-1R); Pheochromocytomas (PHEOs); PET; 68Ga; Exendin-4 | ||
Published online: 29-Jan-2020 | ||
Year: 2020, Volume: 67, Issue: 1 | Page From: 27, Page To: 36 | |
doi:10.4149/neo_2019_190227N163 |
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