In vitro studies have demonstrated the membrane potential dependent enhance
d uptake of phosphonium salts, including [H-3]triphenylmethylphosphonium (T
PMP), into mitochondria of carcinoma and glioma-derived tumor cells, sugges
ting the potential use of phosphonium salts as tracers for tumor imaging. T
his study characterizes the in vivo uptake of [C-11]TPMP in canine brain gl
ioma using PET. Methods: Dynamic paired PET studies of [C-11]TPMP followed
by [Ga-68]ethylenediaminetetraacetic acid (EDTA) were performed 4 d before
and 9 d after tumor cell inoculation. Graphical analysis was used to evalua
te [C-11]TPMP retention in tumor tissue. Distribution of tracer uptake was
compared with tumor histological sections. Results: [C-11]TPMP exhibited en
hanced uptake and prolonged retention in tumor cells. Patlak plot was linea
r over the 20- to 95-min postinjection period (r = 0.97 +/- 0.1). [Ga-68]ED
TA exhibited a gradual washout from the tumor tissue. The tumor-to-normal b
rain uptake ratio at 55 to 95 min postinjection was 47.5 for [C-11]TPMP and
8.1 for [Ga-68]EDTA. Qualitative comparison with histological sections ind
icated that [C-11]TPMP enhanced uptake was restricted to the tumor area. Co
nclusion: The enhanced uptake and prolonged retention in tumor suggest [C-1
1]TPMP as a promising means for imaging of gliomas in dogs. The need for st
udies in humans is indicated.