Tumor Dosimetry Using [124I]m-iodobenzylguanidine MicroPET/CT for [131I]m-iodobenzylguanidine Treatment of Neuroblastoma in a Murine Xenograft Model

Purpose: [I-124]m-iodobenzylguanidine (I-124-mIBG) provides a quantitative tool for pretherapy tumor imaging and dosimetry when performed before [I-131]m-iodobenzylguanidine (I-131-mIBG) targeted radionuclide therapy of neuroblastoma. I-124 (T-1/2 = 4.2 days) has a comparable half-life to that of I-131 (T-1/2 = 8.02 days) and can be imaged by positron emission tomography (PET) for accurate quantification of the radiotracer distribution. We estimated expected radiation dose in tumors from I-131-mIBG therapy using I-124-mIBG microPET/CT imaging data in a murine xenograft model of neuroblastoma transduced to express high levels of the human norepinephrine transporter (hNET). Procedures: In order to enhance mIBG uptake for in vivo imaging and therapy, NB 1691-luciferase (NB1691) human neuroblastoma cells were engineered to express high levels of hNET protein by lentiviral transduction (NB1691-hNET). Both NB1691 and NB1691-hNET cells were implanted subcutaneously and into renal capsules in athymic mice. I-124-mIBG (4.2-6.5 MBq) was administered intravenously for microPET/CT imaging at 5 time points over 95 h (0.5, 3-5, 24, 48, and 93-95 h median time points). In vivo biodistribution data in normal organs, tumors, and whole-body were collected from reconstructed PET images corrected for photon attenuation using the CT-based attenuation map. Organ and tumor dosimetry were determined for I-124-mIBG. Dose estimates for I-131-mIBG were made, assuming the same in vivo biodistribution as I-124-mIBG. Results: All NB1691-hNET tumors had significant uptake and retention of I-124-mIBG, whereas unmodified NB1691 tumors did not demonstrate quantifiable mIBG uptake in vivo, despite in vitro uptake. I-124-mIBG with microPET/CT provided an accurate three-dimensional tool for estimating the radiation dose that would be delivered with I-131-mIBG therapy. For example, in our model system, we estimated that the administration of I-131-mIBG in the range of 52.8-206 MBq would deliver 20 Gy to tumors. Conclusions: The overexpression of hNET was found to be critical for I-124-mIBG uptake and retention in vivo. The quantitative I-124-mIBG PET/CT is a promising new tool to predict tumor radiation doses with I-131-mIBG therapy of neuroblastoma. This methodology may be applied to tumor dosimetry of I-131-mIBG therapy in human subjects using I-124-mIBG pretherapy PET/CT data.