Preclinical evaluation of 18F-LMI1195 for in vivo imaging of pheochromocytoma in the MENX tumor model

Abstract

We evaluated 18F-LMI1195 (1-(3-bromo-4-(3-18F-fluoro- propoxy)benzyl) guanidine), a metaiodobenzylguanidine (MIBG) analog, for the detection of pheochromocytoma in a preclinical in vivo model of endogenous neuroendocrine tumors (multiple endocrine neoplasia [MENX]). Methods: Adrenal uptake kinetics of 18F-LMI1195 were evaluated in healthy Wistar rats (n 5 6) by dynamic PET imaging. Distribution of 18F-LMI1195 was evaluated in tumor-bearing MENX mut/mut rats (n 5 10) and control MENX wild-type rats (n = 4) by biodistribution studies and PET imaging. Biodistribution of 18FLMI1195 was compared with 123I-MIBG in MENX mut/mut rats (n = 6) and correlated with histological tumor volume and norepinephrine transporter (NET) expression. Uptake specificity was evaluated by in vivo inhibition of the NET by desipramine (n = 6). Intraadrenal distribution of 18F-LMI1195 was evaluated by autoradiography. Results: 18F-LMI1195 showed rapid tracer accumulation in adrenal glands 1 min after tracer injection. Adrenal glands of MENX mut/mut animals showed significantly higher standardized uptake value than MENX wild-type controls (maximum SUV, 10.3 ± 2.3 vs. 6.1 ± 0.9, P < 0.01). Adrenal uptake in MENX mut/mut rats could be inhibited by desipramine, shown by biodistribution studies (0.06 ± 0.01 vs. 0.16 ± 0.05 percentage injected dose, P < 0.01), PET imaging (maximum SUV, 3.8 ±0.8 vs. 10.3 ±2.3, P < 0.01), and autoradiography. Adrenal uptake of 18F-LMI1195 correlated with 123I-MIBG uptake (r = 0.91), histological tumor volume (r = 0.68), and NET expression (r = 0.50). 18F-LMI1195 showed an overall favorable distribution for tumor imaging. Conclusion: 18F-LMI1195 shows high and specific accumulation in pheochromocytomas. Its favorable biodistribution makes it a promising PET tracer for tumor imaging. Further studies are warranted to evaluate its clinical value in oncologic indications. COPYRIGHT © 2013 by the Society of Nuclear Medicine and Molecular Imaging, Inc.