Choline transporter as a novel target for molecular imaging of cancer

Toshihiko Hara, Aditya Bansal, Timothy R DeGrado

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

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
Volume5
Issue number4
DOIs
StatePublished - Oct 2006
Externally publishedYes

Fingerprint

Molecular imaging
Molecular Imaging
Choline
Hemicholinium 3
Tumors
Bearings (structural)
Neoplasms
Molecular Probes
Rats
Cells
Glioma
Liver
Muscle
Sodium
choline transporter
Blood
Magnetic resonance spectroscopy
Lung
Phosphorylcholine
Positron emission tomography

ASJC Scopus subject areas

  • Engineering(all)

Cite this

Choline transporter as a novel target for molecular imaging of cancer. / Hara, Toshihiko; Bansal, Aditya; DeGrado, Timothy R.

In: Molecular Imaging, Vol. 5, No. 4, 10.2006, p. 498-509.

Research output: Contribution to journalArticle

Hara, Toshihiko ; Bansal, Aditya ; DeGrado, Timothy R. / Choline transporter as a novel target for molecular imaging of cancer. In: Molecular Imaging. 2006 ; Vol. 5, No. 4. pp. 498-509.
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