Quantitative receptor-based imaging of tumor proliferation with the sigma-2 ligand [(18)F]ISO-1. PLoS One 2013;8(9):e74188
Date
09/28/2013Pubmed ID
24073202Pubmed Central ID
PMC3779213DOI
10.1371/journal.pone.0074188Scopus ID
2-s2.0-84884477756 (requires institutional sign-in at Scopus site) 46 CitationsAbstract
The sigma-2 receptor is expressed in higher density in proliferating (P) tumor cells versus quiescent (Q) tumor cells, thus providing an attractive target for imaging the proliferative status (i.e., P:Q ratio) of solid tumors. Here we evaluate the utility of the sigma-2 receptor ligand 2-(2-[(18)F]fluoroethoxy)-N-(4-(3,4-dihydro-6,7-dimethoxyisoquinolin-2(1H)-yl)butyl)-5-methyl-benzamide, [(18)F]ISO-1, in two different rodent models of breast cancer. In the first study, small animal Positron Emission Tomography (PET) imaging studies were conducted with [(18)F]ISO-1 and (18)FDG in xenografts of mouse mammary tumor 66 and tracer uptake was correlated with the in vivo P:Q ratio determined by flow cytometric measures of BrdU-labeled tumor cells. The second model utilized a chemically-induced (N-methyl-N-nitrosourea [MNU]) model of rat mammary carcinoma to correlate measures of [(18)F]ISO-1 and FDG uptake with MR-based volumetric measures of tumor growth. In addition, [(18)F]ISO-1 and FDG were used to assess the response of MNU-induced tumors to bexarotene and Vorozole therapy. In the mouse mammary 66 tumors, a strong linear correlation was observed between the [(18)F]ISO-1 tumor: background ratio and the proliferative status (P:Q ratio) of the tumor (R = 0.87). Similarly, measures of [(18)F]ISO-1 uptake in MNU-induced tumors significantly correlated (R = 0.68, P<0.003) with changes in tumor volume between consecutive MR imaging sessions. Our data suggest that PET studies of [(18)F]ISO-1 provide a measure of both the proliferative status and tumor growth rate, which would be valuable in designing an appropriate treatment strategy.
Author List
Shoghi KI, Xu J, Su Y, He J, Rowland D, Yan Y, Garbow JR, Tu Z, Jones LA, Higashikubo R, Wheeler KT, Lubet RA, Mach RH, You MMESH terms used to index this publication - Major topics in bold
Alkylating AgentsAnimals
Anticarcinogenic Agents
Apoptosis
Benzamides
Blotting, Western
Cell Proliferation
Female
Flow Cytometry
Fluorodeoxyglucose F18
Humans
Image Processing, Computer-Assisted
Ligands
Mammary Neoplasms, Animal
Methylnitrosourea
Mice
Positron-Emission Tomography
Radiopharmaceuticals
Rats
Receptors, sigma
Tetrahydronaphthalenes
Triazoles
Tumor Cells, Cultured
