Introduction: Near-infrared fluorescence (NIRF) imaging is a promising non-invasive, real-time, sensitive, high-resolution modality for cancer detection due to high tissue penetrance and low background autofluorescence. However, accurate fluorescence quantitation is problematic due to photon scattering by tissues, photon absorption by pigments and water, and static quenching of close-proximity fluorophores. CLR1502 is a NIRF-labeled cancer-specific alkylphosphocholine analog with selective uptake and retention in over 60 preclinical cancer models (including GBM cancer stem cell and brain met models), and approaching clinical trials. To address many of NIRF limitations, we synthesized Iodo-1502, a novel dual-labeled (DL) positron emission tomography (PET) NIRF agent by adding radiolabeled iodine to CLR1502, enabling simultaneous whole-body cancer staging and intraoperative tumor illumination with a single agent. Initial preclinical in vivo studies of Iodo-1502 will be presented.
Methods: Standard organic synthetic chemistry & biology methods. Multiple human cancer lines were implanted for tumor xenografts in athymic nude mice. Once tumors reached 3mm diameter, IV injection of dual-labeled Iodo-1502 and animal imaging up to 120h with IVIS Spectrum (excitation=745nm, emission=800nm) or small animal Siemens Inveon Hybrid PET/CT scanner was done. Tumors were then removed for similar ex vivo quantitative IVIS and PET studies.
Results: Like the NIRF CLR1502 predecessor, the new dual-labeled Iodo-1502 showed striking tumor selectivity and retention for at least 6 days post injection in xenograft models. Moreover, ex vivo quantitation showed excellent correlation of fluorescence and PET imaging.
Conclusions: This new agent overcomes many NIRF limitations, and enables broad spectrum cancer-specific intraoperative tumor margin illumination and whole-body quantitative PET imaging.
Patient Care: Improve technology for cancer imaging and intraoperative tumor visualization
Learning Objectives: To learn about new cancer imaging technology
To demonstrate multimodality intraoperative fluorescence and cancer imaging agents
References: Weichert JP, Clark PA, Kandela IK et al.: Alkylphosphocholine Analogs for Broad-Spectrum Cancer Imaging and Therapy. Science Translational Medicine 6(240), 240ra275 (2014).
Swanson KI, Clark PA, Zhang RR et al.: Fluorescent Cancer-Selective Alkylphosphocholine Analogs for Intraoperative Glioma Detection. Neurosurgery 76(2), 115-124 (2015).