Faculty Collaboration Database

A (99m)Tc-labeled triphenylphosphonium derivative for the early detection of breast tumors. Cancer Biother Radiopharm 2009 Oct;24(5):579-87

Date

11/03/2009

Pubmed ID

19877888

Pubmed Central ID

PMC2883499

DOI

10.1089/cbr.2008.0606

Scopus ID

2-s2.0-70449135470 (requires institutional sign-in at Scopus site)   21 Citations

Abstract

INTRODUCTION: A greater mitochondrial membrane potential in tumor cells has been shown to enhance the accumulation of triphenyl phosphonium derivatives. The aim of this study was to synthesize and characterize (99m)Tc-labeled alkyl triphenyl phosphonium ((99m)Tc-Mito(10)-MAG3) for the early detection of breast tumors.

METHODS: Mito(10)-MAG3 was synthesized by coupling (10-aminodecyl)triphenyl phosphonium bromide with NHS-MAG3 and radiolabeled with (99m)Tc. Biodistribution and pharmacokinetics of (99m)Tc-Mito(10)-MAG3 was investigated in female Sprague-Dawley rats. Initially, (99m)Tc-Mito(10)-MAG3 was tested in animals with established breast tumors. In a subsequent longitudinal study, the imaging efficacy of (99m)Tc(10)-Mito-MAG3 for detecting small, nonpalpable breast tumors was assessed after chemically inducting breast carcinoma. Tumors detected by imaging were allowed to grow to palpable size and confirmed by histology. The results were compared with (99m)Tc-MIBI.

RESULTS: The synthesis of Mito(10)-MAG3 was confirmed by mass spectrometry. The compound was radiolabeled with (99m)Tc to > 92% in a single step. The radiopharmaceutical exhibited fast blood clearance and low cardiac uptake. In the initial study, using animals with established breast tumors, (99m)Tc-Mito(10)-MAG3 imaging detected small lesions that were missed by palpation. In the longitudinal study, (99m)Tc-Mito(10)-MAG3 exhibited focal uptake in small breast tumors, which were confirmed by histology.

CONCLUSIONS: Imaging, using (99m)Tc-Mito(10)-MAG3, allowed the early detection of small neoplastic lesions in the mammary glands. The agent significantly reduced cardiac uptake, compared with (99m)Tc-MBIB. The phosphonium-based derivatives warrant further characterization and development as imaging agents for scintimammography.

Author List

Li Z, Lopez M, Hardy M, McAllister DM, Kalyanaraman B, Zhao M

Authors

Micael Joel Hardy PhD Visiting Assistant Professor in the Biophysics department at Medical College of Wisconsin
Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Breast Neoplasms
Disease Models, Animal
Early Detection of Cancer
Female
Membrane Potential, Mitochondrial
Mitochondria
Models, Chemical
Neoplasm Transplantation
Radionuclide Imaging
Radiopharmaceuticals
Rats
Rats, Sprague-Dawley
Technetium
Technetium Tc 99m Sestamibi