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. [(3)H]
Choline uptake by PC-3 cells was found to have both facilitative and nonfacilitative components. Facilitative transport was characterized by partial
sodium dependence and intermediate affinity (K(M) = 9.7 +/- 0.8 microM). HC-3 inhibited
choline with a K(I) of 10.5+/- 2.2 microM.
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 [(3)H]HC-3 to PC-3 cells was rapid and specific (competitively blocked with unlabeled HC-3). Biodistribution of [(3)H]HC-3 in 9L
glioma-bearing rats showed the ranking of uptake to be kidney > lung >
tumor > liver > skeletal muscle congruent with blood > brain. In comparison with [(14)C]
choline, [(3)H]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 [(3)H]HC-3 in
tumor-bearing rats encourage the development of molecular imaging probes based on
choline transporter binding
ligands.