A 99mTc-Labeled Triphenylphosphonium Derivative for the Early Detection of Breast Tumors

Zhixin Li, Marcos Lopez, Micaël Hardy, Donna M. McAllister, Balaraman Kalyanaraman, Ming Zhao*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


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 99mTc- labeled alkyl triphenyl phosphonium (99mTc-Mito10-MAG3) for the early detection of breast tumors. Methods: Mito10-MAG3 was synthesized by coupling (10-aminodecyl)triphenyl phosphonium bromide with NHS-MAG3 and radiolabeled with 99mTc. Biodistribution and pharmacokinetics of 99mTc-Mito10-MAG3 was investigated in female Sprague-Dawley rats. Initially, 99mTc-Mito10-MAG3 was tested in animals with established breast tumors. In a subsequent longitudinal study, the imaging efficacy of 99mTc10-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 99mTc-MIBI. Results: The synthesis of Mito10-MAG3 was confirmed by mass spectrometry. The compound was radiolabeled with 99mTc 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, 99mTc-Mito10-MAG3 imaging detected small lesions that were missed by palpation. In the longitudinal study, 99mTc-Mito10-MAG3 exhibited focal uptake in small breast tumors, which were confirmed by histology. Conclusions: Imaging, using 99mTc-Mito10-MAG3, allowed the early detection of small neoplastic lesions in the mammary glands. The agent significantly reduced cardiac uptake, compared with 99mTc-MBIB. The phosphonium-based derivatives warrant further characterization and development as imaging agents for scintimammography.

Original languageEnglish (US)
Pages (from-to)579-587
Number of pages9
JournalCancer Biotherapy and Radiopharmaceuticals
Issue number5
StatePublished - Oct 1 2009


  • Breast cancer
  • DMBA
  • Mitochondria
  • Scintimammography

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology
  • Cancer Research


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