title: Preclinical evaluation of 18F-LMI1195 for in vivo imaging of pheochromocytoma in the MENX tumor model.
abstract: We evaluated (18)F-LMI1195 (1-(3-bromo-4-(3-(18)F-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 (18)F-LMI1195 were evaluated in healthy Wistar rats (n = 6) by dynamic PET imaging. Distribution of (18)F-LMI1195 was evaluated in tumor-bearing MENX mut/mut rats (n = 10) and control MENX wild-type rats (n = 4) by biodistribution studies and PET imaging. Biodistribution of (18)F-LMI1195 was compared with (123)I-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 (18)F-LMI1195 was evaluated by autoradiography.
  
  
  RESULTS
  (18)F-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 (18)F-LMI1195 correlated with (123)I-MIBG uptake (r = 0.91), histological tumor volume (r = 0.68), and NET expression (r = 0.50). (18)F-LMI1195 showed an overall favorable distribution for tumor imaging.
  
  
  CONCLUSIONS
  (18)F-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.
authors.affiliation: Klinikum Rechts der Isar der Technischen Universität München, Nuklearmedizinische Klinik, München, Germany.
authors.forename: Florian C
authors.initials: FC
authors.lastname: Gaertner
authors.forename: Tobias
authors.initials: T
authors.lastname: Wiedemann
authors.forename: Behrooz H
authors.initials: BH
authors.lastname: Yousefi
authors.forename: Misu
authors.initials: M
authors.lastname: Lee
authors.forename: Ines
authors.initials: I
authors.lastname: Repokis
authors.forename: Takahiro
authors.initials: T
authors.lastname: Higuchi
authors.forename: Stephan G
authors.initials: SG
authors.lastname: Nekolla
authors.forename: Ming
authors.initials: M
authors.lastname: Yu
authors.forename: Simon
authors.initials: S
authors.lastname: Robinson
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaiger
authors.forename: Natalia S
authors.initials: NS
authors.lastname: Pellegata
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D000818:Animals; D001345:Autoradiography; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005462:Fluorine Radioisotopes; D005464:Fluorobenzenes / Q000493:pharmacokinetics; D015972:Gene Expression Regulation, Neoplastic; D006146:Guanidines / Q000493:pharmacokinetics; D009377:Multiple Endocrine Neoplasia; D009154:Mutation; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics; D009929:Organ Size; D010673:Pheochromocytoma / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D049268:Positron-Emission Tomography; D051381:Rats; D047368:Tumor Burden
chemical_list: D005462:Fluorine Radioisotopes; D005464:Fluorobenzenes; D006146:Guanidines; D050484:Norepinephrine Plasma Membrane Transport Proteins; C561360:flubrobenguane
keywords: 18F-LMI1195; MENX; MIBG; oncology; pheochromocytoma