Relative biodistribution and tumor uptake of 124I-CLR1404 (aka NM404) in non-small cell lung cancer (NSCLC) patients

Objectives CLR1404 is a diapeutic phospholipid ether analogue that enters malignant cells via overexpressed membrane lipid rafts. The aim of this study is to demonstrate the biodistribution and tumor uptake of 124ICLR1404 in patients with NSCLC.

Methods Five patients with NSCLC were administered 111-185 MBq of 124I-CLR1404. Whole body PET/CT scans were obtained at multiple time points and baseline FDG PET scans were obtained. Qualitative & quantitative analyses of major organs and malignant tumors were performed.

Results Normal organ biodistribution and clearance of 124I-CLR1404 in all 5 patients was uniform. Early activity was highest in the blood pool followed by the liver and spleen. No uptake was detected in the normal brain.124I-CLR1404 uptake was detected in multiple malignant lesions that demonstrated prolonged retention that increased over time. Concordant lesions: Both FDG and CLR1404 avid lesions were identified in the lung, T2 vertebra, scapula and an axillary lymph node. These lesions were detected on CLR1404 PET by 24 to 48h. Both scans were negative in one patient without active malignancy. Discordant lesions: In one patient, 3 brain metastases were intensely avid on CLR1404 and were not hypermetabolic on the FDG PET. One patient showed FDG avid pulmonary lesions and a supraclavicular nodal lesion that were not avid on CLR1404 PET and in a separate patient an FDG avid hepatic lesion was less avid on CLR1404.

Conclusions This is an early report demonstrating normal organ biodistribution and prolonged tumor uptake of 124I-CLR1404 in patients with lung cancer. Compared with FDG, there were multiple concordant and several discordant lesions with CLR1404 uptake, including striking CLR1404 avidity of cerebral metastases that were not hypermetabolic with FDG. Further trials with this exciting new agent are currently underway.

Research Support Novelos Therapeutics, Inc