A 68Ga-Substituted Keggin Phosphotungstate as an Intrinsically Radiolabeled Inorganic PET Tracer for Cell Tracking.

Abstract

Polyoxometalates (POMs) offer unique physicochemical properties for radiopharmaceutical design, yet their integration with clinically relevant radionuclides remains largely unexplored. Here we report the isolation and comprehensive solid-state and solution characterization of the gallium-substituted Keggin phosphotungstate cesium salt, Cs4[Ga(H2O)PW11O39]·8H2O (CsGaPW11), including single-crystal and powder X-ray diffraction, multinuclear NMR (31P, 71Ga, 183W), IR spectroscopy, ESI-MS, elemental analysis, and TGA. The radiolabeled analogue Cs68GaPW11 (45-55 MBq, >96% radiochemical purity) was synthesized in under 60 min, dictated by the 68 min half-life of 68Ga, and retained full structural integrity after radioactive decay. In CHO-K1 cells, Cs68GaPW11 shows higher cellular uptake than 68GaCl3 and 68Ga-oxine, with radioactivity progressively shifting from the cell membrane to the intracellular compartment over 60 min. Together with low cytotoxicity (>90% viability at 100 µM), these findings identify the membrane-permeable Keggin anion as a viable inorganic platform for PET cell tracking.

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