TY - JOUR T1 - Tetraphenylphosphonium as a Novel Molecular Probe for Imaging Tumors JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 636 LP - 643 VL - 45 IS - 4 AU - Jung-Jun Min AU - Sandip Biswal AU - Christophe Deroose AU - Sanjiv S. Gambhir Y1 - 2004/04/01 UR - http://jnm.snmjournals.org/content/45/4/636.abstract N2 - Mitochondrial membrane potential (ΔΨm)–dependent enhanced uptake of phosphonium salts, including 3H-tetraphenylphosphonium (3H-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 3H-TPP and compare it with 18F-FDG in cell culture and in xenograft, metastatic, and inflammation models in living animals. Methods: 3H-TPP and 3H-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 3H-TPP and 18F-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 3H-TPP and 18F-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 ΔΨm data from a separate study and the current 3H-TPP uptake data showed good correlation (r2 = 0.82, P < 0.05). 3H-TPP accumulation was significantly greater than that of 3H-FDG for glucose ≥100 mg/dL. The biodistribution study of 3H-TPP showed low uptake in most tissues but high accumulation in the heart and kidneys. 3H-TPP accumulation in xenograft or metastatic tumors was comparable with that of 18F-FDG, whereas 3H-TPP accumulation in inflammatory tissues was markedly lower than that of 18F-FDG. Conclusion: The sensitive tumor accumulation of 3H-TPP with less propensity for inflammatory regions warrants further investigation of radiolabeled phosphonium analogs for tumor imaging in living subjects. ER -