CONTEXT: NM404 is a second-generation radioiodinated phospholipid ether analog that undergoes prolonged and selective retention in a wide variety of malignant tumors in animal models. The compound takes advantage of an apparent lack of metabolic alkyl cleavage enzyme activity in tumor cells relative to normal cells. The aim of this project was to examine the tumor uptake and retention properties of NM404 in human non-small cell lung cancer (NSCLC).
RESULTS: Iodine-131-labeled NM404 was injected into patients with advanced NSCLC. The patients were scanned with a dual-head SPECT scanner at three, six, 24, 48, and 96 hours and at seven and 11 days. Qualitative imaging results indicated that I-131-labeled NM404 clearly localizes in bilateral pulmonary masses as early as 24 hours after injection and is selectively retained in the tumors for more than 11 days. Background radioactivity in the liver and lower abdominal region was significantly less than was observed previously with the predecessor agent NM324. No adverse reactions occurred in any of the patients.
IMPLICATIONS: The findings suggest that NM404 exhibits tumor uptake and retention properties in human NSCLC similar to those seen previously in rodent models. Efforts are under way to extend the utility of NM404 to PET imaging by incorporation with I-124, a positron isotope with a four-day half-life. Because of the selective and prolonged retention of NM404 in tumor cells, studies also are evaluating the radiotherapeutic potential of the agent.
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