Author:

Keywords:

mitochondrial membrane potential, tetraphenylphosphonium, fdg, pet, reporter gene-expression, carcinoma-cells, high accumulation, rhodamine-123, invitro, tissue, mice, fluorine-18-fluorodeoxyglucose, biodistribution, Science & Technology, Life Sciences & Biomedicine, Radiology, Nuclear Medicine & Medical Imaging, FDG, PET, REPORTER GENE-EXPRESSION, CARCINOMA-CELLS, HIGH ACCUMULATION, RHODAMINE-123, INVITRO, TISSUE, MICE, FLUORINE-18-FLUORODEOXYGLUCOSE, BIODISTRIBUTION, Animals, Cell Line, Tumor, Diagnosis, Differential, Fluorodeoxyglucose F18, Inflammation, Male, Mice, Mice, Nude, Molecular Probes, Neoplasms, Onium Compounds, Organ Specificity, Organophosphorus Compounds, Rats, Rats, Sprague-Dawley, Reproducibility of Results, Sensitivity and Specificity, Tissue Distribution, Tomography, Emission-Computed, Tuberculosis, Cutaneous, 1103 Clinical Sciences, Nuclear Medicine & Medical Imaging, 3202 Clinical sciences

Abstract:

Mitochondrial membrane potential (DeltaPsim)-dependent enhanced uptake of phosphonium salts, including H-3-tetraphenylphosphonium (H-3-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 H-3-TPP and compare it with F-18-FDG in cell culture and in xenograft, metastatic, and inflammation models in living animals. Methods: H-3-TPP and H-3-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 H-3-TPP and F-18-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 H-3-TPP and F-18-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 H-3-TPP uptake data showed good correlation (r(2) = 0.82, P < 0.05). H-3-TPP accumulation was significantly greater than that of H-3-FDG for glucose 100 mg/dL. The biodistribution study of H-3-TPP showed low uptake in most tissues but high accumulation in the heart and kidneys. H-3-TPP accumulation in xenograft or metastatic tumors was comparable with that of F-18-FDG, whereas H-3-TPP accumulation in inflammatory tissues was markedly lower than that of F-18-FDG. Conclusion: The sensitive tumor accumulation of H-3-TPP with less propensity for inflammatory regions warrants further investigation of radiolabeled phosphonium analogs or tumor imaging in living subjects.