Choline transporter as a novel target for molecular imaging of cancer

Toshihiko Hara, Aditya Bansal, Timothy R. DeGrado

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


Abnormalities of choline processing in cancer cells have been used as a basis for imaging of cancer with positron emission tomography and magnetic resonance spectroscopy. In this study, the transport mechanism for choline was investigated in cultured PC-3 prostate cancer cells. Furthermore, tritiated hemicholinium 3 (HC-3), a well-known inhibitor of choline transport, was studied as a prototypic molecular imaging probe in PC-3 cells and 9L glioma-bearing rats. [3H]Choline uptake by PC-3 cells was found to have both facultative and nonfacilitative components. Facultative transport was characterized by partial sodium dependence and intermediate affinity (K M = 9.7 ± 0.8 μM). HC-3 inhibited choline with a K I of 10.5± 2.2 μM. Ouabain (1 mM) caused a 94% reduction in choline uptake. At physiologic choline concentration, phosphocholine was the rapid and predominant metabolic fate. The binding of [3H]HC-3 to PC-3 cells was rapid and specific (competitively blocked with unlabeled HC-3). Biodistribution of [3H]HC-3 in 9L glioma-bearing rats showed the ranking of uptake to be kidney > lung > tumor > liver > skeletal muscle ≈ blood > brain. In comparison with [14C]choline, [ 3H]HC-3 showed over twofold higher tumor uptake and favorable uptake ratios of tumor to blood, tumor to muscle, tumor to lung, and tumor to liver. The data demonstrate the quantitative importance of an intermediate-affinity, partially sodium-dependent choline transport system on choline processing in PC-3 cancer cells. The biodistribution properties of [3H]HC-3 in tumor-bearing rats encourage the development of molecular imaging probes based on choline transporter binding ligands.

Original languageEnglish (US)
Pages (from-to)498-509
Number of pages12
JournalMolecular Imaging
Issue number4
StatePublished - Oct 2006

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Biomedical Engineering
  • Radiology Nuclear Medicine and imaging
  • Condensed Matter Physics


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