Abstract
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Objectives The sigma-2 PET ligand [18F]ISO-1 has shown promise in preclinical imaging studies in animal models of cancer. The goal of the current study was to determine the correlation between tumor uptake of [18F]ISO-1 and histological measures of cell proliferation in cancer patients.
Methods PET imaging studies were conducted on a CTI/Siemens Biograph-40 PET/CT scanner in patients with breast cancer (N = 13), head & neck (H&N) cancer (N = 10) and lymphoma (N = 7). Patients were injected with ~8 mCi (296 MBq) of [18F]ISO-1. PET images were evaluated using maximum standardized uptake value (SUVmax), tumor: muscle (T/M) ratio, and Logan graphical analysis. The degree of uptake of [18F]ISO-1 was compared with histological measures of cell proliferation (Ki-67 and mitotic index) in 28 of the 30 patients studied. All patients underwent vital signs measurements, clinical laboratory testing and electrocardiography before [18F]ISO-1 administration, as well as during and after completion of imaging.
Results There was a high variability in uptake of [18F]ISO-1 in tumors, as expected with a radiotracer that measures the proliferative status of solid tumors. [18F]ISO-1 uptake was observed in the primary tumors; lymph node involvement was observed in lymphoma. In addition, [18F]ISO-1 uptake in lymph node and bone marrow was noted in metastatic disease. The best correlation between [18F]ISO-1 uptake and histological measures of cell proliferation was observed when comparing the T/M ratio at 1 hr post-injection of the tracer with the Ki-67 labeling index (p = 0.011). The patients could be stratified into groups of low (Ki-67 < 0.45; T/M = 3.06 ± 1.17) versus high proliferative status (Ki-67 > 0.45; T/M = 5.35 ± 3.59; p = 0.02). No adverse effects of [18F]ISO-1 were encountered.
Conclusions Our results suggest that [18F]ISO-1 is a promising radiotracer for imaging the proliferative status of solid tumors. Expanded studies with this radiotracer in cancer patients are clearly warranted.
Research Support Funded by Isotrace Technologies, Inc