Phospholipid ether analogs for the detection of colorectal cancers.

Abstract

486 Background: The treatment of pts with localized colorectal cancer (CRC) depends on the resection of the primary tumor with adequate margins and sufficient lymph node sampling. A novel imaging agent that accumulates in CRCs and regional lymph nodes is needed. Novelos, Inc. has developed a new phospholipid ether analog therapeutic and diagnostic platform. Molecules from this platform have shown to preferentially accumulate in multiple cancer types. CLR1502 is a near-infrared fluorescent labeled phospholipid ether analog, whereas 124/131I-CLR1404 is under clinical investigation as a PET tracer or a therapeutic agent imaged by SPECT. We investigated the use of CLR1502 for the detection of intestinal cancers in a murine model and 131I-CLR1404 in human metastatic CRC. Methods: Mice with loss of APC and a constitutively active PI3K in the distal small intestine and colon develop multiple intestinal tumors ranging from benign adenomas to locally advanced adenocarcinomas. These mice were injected intravenously with CLR1502. At necropsy 96 hours after injection, the intestine was removed and tumors were analyzed using a Spectrum IVIS Caliper Life Science Imager and Fluobeam Handheld Imager. The intensity of the fluorescent signal was correlated with the histological characteristics for each individual intestinal tumor. In addition, SPECT imaging with 131I-CLR404 was performed as part of a clinical trial in patients with advanced solid tumors. Results: Colon adenocarcinomas demonstrated increased accumulation of CLR1502 compared to non-invasive lesions (total radiant efficiency: 1.76E+10 vs 3.27E+9 respectively, p=0.027). Metastatic spread to the mesentery and mesenteric lymph nodes was detected with near-infrared fluorescent imaging. Similarly, 131I-CLR1404 was shown to accumulate in metastatic tumors in a patient with colorectal adenocarcinoma. Conclusions: CLR1502 and 124/131I-CLR1404 hold great promise for enhancing our ability to treat CRC. CLR1502 may enhance our ability to properly resect CRCs through better localization of the primary tumor and improve staging through the identification of involved lymph nodes. 124/131I-CLR1404 has the advantage of detecting distant disease.