Tetraphenylphosphonium as a novel molecular probe for imaging tumors.
Mitochondrial membrane potential (DeltaPsim)-dependent enhanced uptake of phosphonium salts, including (3)H-tetraphenylphosphonium ((3)H-TPP), in tumor cells, suggests the potential use of phosphonium salts as tracers for tumor imaging. In this study, we characterize the tumor accumulation of (3)H-TPP and compare it with (18)F-FDG in cell culture and in xenograft, metastatic, and inflammation models in living animals.


METHODS
(3)H-TPP and (3)H-FDG accumulation was compared in cell culture with a variety of cell lines in different glucose concentrations. Normal biodistribution and tumor uptake were assessed using nude mice with or without subcutaneous xenograft tumors (C6). To compare the accumulation of (3)H-TPP and (18)F-FDG in a metastatic tumor, severe combined immunodeficiency mice were tail-vein injected with human melanoma cell lines (A375-FL). To characterize the accumulation of (3)H-TPP and (18)F-FDG in inflammation, an inflammatory reaction was induced by subcutaneous injection of Complete Freund's Adjuvant in the left hind paw of Sprague-Dawley rat.


RESULTS
The DeltaPsim data from a separate study and the current (3)H-TPP uptake data showed good correlation (r(2) = 0.82, P < 0.05). (3)H-TPP accumulation was significantly greater than that of (3)H-FDG for glucose >/=100 mg/dL. The biodistribution study of (3)H-TPP showed low uptake in most tissues but high accumulation in the heart and kidneys. (3)H-TPP accumulation in xenograft or metastatic tumors was comparable with that of (18)F-FDG, whereas (3)H-TPP accumulation in inflammatory tissues was markedly lower than that of (18)F-FDG.


CONCLUSIONS
The sensitive tumor accumulation of (3)H-TPP with less propensity for inflammatory regions warrants further investigation of radiolabeled phosphonium analogs for tumor imaging in living subjects.
Min
Jung-Jun
JJ
Department of Radiology and the Bio-X Program, Stanford University School of Medicine, Stanford, California, USA.
Biswal
Sandip
S
Deroose
Christophe
C
Gambhir
Sanjiv S
SS
D000818:Animals; D045744:Cell Line, Tumor / Q000000981:diagnostic imaging / Q000378:metabolism; D003937:Diagnosis, Differential; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D007249:Inflammation / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D015335:Molecular Probes / Q000493:pharmacokinetics; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D009861:Onium Compounds / Q000493:pharmacokinetics*; D009928:Organ Specificity; D009943:Organophosphorus Compounds / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods*; D014382:Tuberculosis, Cutaneous / Q000000981:diagnostic imaging / Q000378:metabolism
D015335:Molecular Probes; D009861:Onium Compounds; D009943:Organophosphorus Compounds; D019788:Fluorodeoxyglucose F18; C013289:tetraphenylphosphonium