Comparison of the sigma-2 receptor radiotracer, [¹⁸F]ISO-1, with the thymidine analogs [¹⁸F]FLT and [¹⁸F]FMAU for imaging the proliferative status of solid tumors

Objectives Solid tumors consist of cells that are either proliferating (P) or driven into quiescence (Q) by hypoxia and nutrient deprivation. The P:Q ratio is an important parameter in determining an appropriate strategy for treating tumors. The goal of this study was to compare the sigma-2 receptor radiotracer, [¹⁸F]ISO-1, with the thymidine analogs [¹⁸F]FLT and [¹⁸F]FMAU to ascertain which radiotracer is best suited for determining a patient’s tumor P:Q ratio.

Methods Mouse mammary (66) cells were bilaterally implanted in nude mice. Once tumors reached 0.5 - 1.2 g, mice were injected IP with 100 mg/kg of BrdU every 8 h beginning 48 h prior to microPET studies with ISO-1, FLT or FMAU. MicroPET studies were performed 1 h after radiotracer injection. Mice were euthanized after imaging, tumors were dissociated into a single cell suspensions, and the P:Q ratio of each tumor determined by flow cytometry. MicroPET data were compared to the BrdU P:Q ratio for each tumor.

Results MicroPET studies of ISO-1 resulted in clear images of tumors and high tumor (T) : normal tissue (NT) ratios. The T:NT ratios of FLT and FMAU were lower than that of ISO-1. The T:NT ratios of ISO-1 also showed a clinically-relevant correlation with the tumor P:Q ratio (R² = 0.66); no clinically-relevant correlation was found for FLT or FMAU.

Conclusions These data indicate that the sigma-2 receptor radiotracer, [¹⁸F]ISO-1, is likely to provide the best estimate of the P:Q ratio of human solid tumors with PET.

Research Support Funded by NCI, Isotrace and Bayer-Schering.