Clinical Imaging and Dosimetry of a Pan-Cancer Targeting Alkylphosphocholine Analog, [124I]I-NM404

Joseph J. Grudzinski, Lance T. Hall, Steve Cho, Glenn Liu, Anne Traynor, Matthew H. Lee, Marc Longino, Anatoly Pinchuk, Christine Jaskowiak, Bryan Bednarz, Jamey Weichert, John S. Kuo
2022 Radiation  
The purpose of this study was to assess organ dosimetry and clinical use of [124I]I-NM404, a radiotheranostic alkylphosphocholine (APC) analog, for accurate detection and characterization of a wide variety of solid primary and metastatic malignancies anywhere in the body. Methods: Patterns of [124I]I-NM404 uptake were quantitatively analyzed and qualitatively compared with [18F]FDG PET/CT in 14 patients (median age, 61.5 years; 7 males, 7 females) with refractory metastatic cancer who were
more » ... led in one of two Phase I imaging studies. Primary cancer types included bronchogenic (n = 7), colorectal (n = 1), prostate (n = 1), triple-negative breast (n = 1), head and neck (n = 2), pancreatic (n = 1) carcinoma, and melanoma (n = 1). Patients were administered [124I]I-NM404 and imaged via PET/CT at 1–2, 4–6, 24, and 48 h and at 5–10 days post injection, from top of the skull to mid-thigh. Volumes of interest were drawn over lungs, heart, liver, kidneys, and whole body for dosimetry estimation using OLINDA 1.1 Representative metastatic index lesions were chosen when applicable for each case with active sites of disease to calculate maximum and mean tumor-to-background ratios (TBRmax, TBRmean), using the adjacent normal organ parenchyma as background when possible. Results: Administrations of [124I]-NM404 were safe and well-tolerated. The organs with the highest estimated absorbed dose (mean ± SD) were the lungs (1.74 ± 0.39 mSv/MBq), heart wall (1.52 ± 0.29 mSv/MBq), liver (1.28 ± 0.21 mSv/MBq) and kidneys (1.09 ± 0.20 mSv/MBq). The effective dose was 0.77 ± 0.05 mSv/MBq. Preferential uptake within metastatic foci was observed with all cancer subtypes, TBRmax ranged from 1.95 to 15.36 and TBRmean ranged from 1.63 to 6.63. Robust sensitive imaging of lesions was enhanced by delayed timing (2–6 days after single injection of [124I]I-NM404, respectively) due to persistent tumor retention coupled with progressive washout of background activity. NM404 uptake was evident in pulmonary, nodal, skeletal, CNS, and other metastatic sites of disease. Radiation related injury or necrosis were NM404 negative, whereas certain small number of metastatic brain lesions were false negative for NM404. Conclusions: In addition to being well tolerated, selective tumor uptake of NM404 with prolonged retention was demonstrated within a broad spectrum of highly treated metastatic cancers.
doi:10.3390/radiation2020015 fatcat:e7ijs6sia5btzjuh2of3zv5nta