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Enhanced Uptake of [¹¹C]TPMP in Canine Brain Tumor: A PET Study

Department of Radiology, Division of Nuclear Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland

Correspondence: For correspondence or reprints contact: Igal Madar, PhD, Division of Nuclear Medicine, Johns Hopkins University School of Medicine, 601 N. Carolina St./JHDC 4230, Baltimore, MD 21282-0855.

ABSTRACT

In vitro studies have demonstrated the membrane potential dependent enhanced uptake of phosphonium salts, including [³H]triphenylmethylphosphonium (TPMP), into mitochondria of carcinoma and glioma-derived tumor cells, suggesting the potential use of phosphonium salts as tracers for tumor imaging. This study characterizes the in vivo uptake of [¹¹C]TPMP in canine brain glioma using PET. Methods: Dynamic paired PET studies of [¹¹C]TPMP followed by [⁶⁸Ga]ethylenediaminetetraacetic acid (EDTA) were performed 4 d before and 9 d after tumor cell inoculation. Graphical analysis was used to evaluate [¹¹C]TPMP retention in tumor tissue. Distribution of tracer uptake was compared with tumor histological sections. Results: [11C]TPMP exhibited enhanced uptake and prolonged retention in tumor cells. Patlak plot was linear over the 20- to 95-min postinjection period (r = 0.97 ± 0.1). [⁶⁸Ga]EDTA exhibited a gradual washout from the tumor tissue. The tumor-to-normal brain uptake ratio at 55 to 95 min postinjection was 47.5 for [¹¹C]TPMP and 8.1 for [⁶⁸Ga]EDTA. Qualitative comparison with histological sections indicated that [¹¹C]TPMP enhanced uptake was restricted to the tumor area. Conclusion: The enhanced uptake and prolonged retention in tumor suggest [¹¹C]TPMP as a promising means for imaging of gliomas in dogs. The need for studies in humans is indicated.

Key Words: [¹¹C]triphenylmethylphosphonium • glioma • dog • PET

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