TY - JOUR
T1 - Phospholipid ether analogs for the detection of colorectal tumors
AU - Deming, Dustin A.
AU - Maher, Molly E.
AU - Leystra, Alyssa A.
AU - Grudzinski, Joseph P.
AU - Clipson, Linda
AU - Albrecht, Dawn M.
AU - Washington, Mary Kay
AU - Matkowskyj, Kristina A.
AU - Hall, Lance T.
AU - Lubner, Sam J.
AU - Weichert, Jamey P.
AU - Halberg, Richard B.
N1 - Publisher Copyright:
©2014 Deming et al.
PY - 2014/10/6
Y1 - 2014/10/6
N2 - The treatment of localized colorectal cancer (CRC) depends on resection of the primary tumor with adequate margins and sufficient lymph node sampling. A novel imaging agent that accumulates in CRCs and the associated lymph nodes is needed. Cellectar Biosciences has developed a phospholipid ether analog platform that is both diagnostic and therapeutic. CLR1502 is a near-infrared fluorescent molecule, whereas 124,131l-CLR1404 is under clinical investigation as a PET tracer/ therapeutic agent imaged by SPECT. We investigated the use of CLR1502 for the detection of Iitestinal cancers in a murine model and 131l-CLR1404 in a patient with metastatic CRC. Mice that develop multiple intestinal tumors ranging from adenomas to locally advanced adenocarcinomas were utilized. After 96 hours post CLR1502 injection, the intestinal tumors were analyzed using a Spectrum lVlS (Perkin Elmer) and a Fluobeam (Fluoptics). The intensity of the fluorescent signal was correlated with the histological characteristics for each tumor. Colon adenocarcinomas demonstrated increased accumulation of CLR1502 compared to non-invasive lesions (total radiant efficiency: 1.76x10lü vs 3.27x109 respectively, p = 0.006). Metastatic mesenteric tumors and uninvolved lymph nodes were detected with CLR1502. In addition, SPECT imaging with 131l-CLR1404 was performed as part ofa clinical trial in patients with advanced solid tumors. 131l-CLR1404 was shown to accumulate in metastatic tumors in a patient with colorectal adenocarcinoma. Together, these compounds might enhance our ability to properly resect CRCs through better localization of the primary tumor and improved lymph node identification as well as detect distant disease.
AB - The treatment of localized colorectal cancer (CRC) depends on resection of the primary tumor with adequate margins and sufficient lymph node sampling. A novel imaging agent that accumulates in CRCs and the associated lymph nodes is needed. Cellectar Biosciences has developed a phospholipid ether analog platform that is both diagnostic and therapeutic. CLR1502 is a near-infrared fluorescent molecule, whereas 124,131l-CLR1404 is under clinical investigation as a PET tracer/ therapeutic agent imaged by SPECT. We investigated the use of CLR1502 for the detection of Iitestinal cancers in a murine model and 131l-CLR1404 in a patient with metastatic CRC. Mice that develop multiple intestinal tumors ranging from adenomas to locally advanced adenocarcinomas were utilized. After 96 hours post CLR1502 injection, the intestinal tumors were analyzed using a Spectrum lVlS (Perkin Elmer) and a Fluobeam (Fluoptics). The intensity of the fluorescent signal was correlated with the histological characteristics for each tumor. Colon adenocarcinomas demonstrated increased accumulation of CLR1502 compared to non-invasive lesions (total radiant efficiency: 1.76x10lü vs 3.27x109 respectively, p = 0.006). Metastatic mesenteric tumors and uninvolved lymph nodes were detected with CLR1502. In addition, SPECT imaging with 131l-CLR1404 was performed as part ofa clinical trial in patients with advanced solid tumors. 131l-CLR1404 was shown to accumulate in metastatic tumors in a patient with colorectal adenocarcinoma. Together, these compounds might enhance our ability to properly resect CRCs through better localization of the primary tumor and improved lymph node identification as well as detect distant disease.
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U2 - 10.1371/journal,pone.0109668
DO - 10.1371/journal,pone.0109668
M3 - Article
C2 - 25286226
SN - 1932-6203
VL - 9
JO - PLoS ONE
JF - PLoS ONE
IS - 10
M1 - e109668
ER -