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

Abstract

Purpose [124I]m-iodobenzylguanidine (124I-mIBG) provides a quantitative tool for pretherapy tumor imaging and dosimetry when performed before [131I]m-iodobenzylguanidine (131I-mIBG) targeted radionuclide therapy of neuroblastoma. 124I (T1/2=4.2d) has a comparable half-life to that of 131I (T1/2=8.02d), and can be imaged by PET for accurate quantification of the radiotracer distribution. We estimated expected radiation dose in tumors from 131I-mIBG therapy using 124I-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. 124I-mIBG (4.2–6.5 MBq) was administered intravenously for microPET/CT imaging at 5 time points over 95 hours (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 124I-mIBG. Dose estimates for 131I-mIBG were made, assuming the same in vivo biodistribution as 124I-mIBG. Results All NB1691-hNET tumors had significant uptake and retention of 124I-mIBG, whereas unmodified NB1691 tumors did not demonstrate quantifiable mIBG uptake in vivo, despite in vitro uptake. 124I-mIBG with microPET/CT provided an accurate 3-dimensional tool for estimating the radiation dose that would be delivered with 131I-mIBG therapy. For example, in our model system, we estimated that the administration of 131I-mIBG in the range of 52.8 – 206 MBq would deliver 20 Gy to tumors. Conclusion The overexpression of hNET was found to be critical for 124I-mIBG uptake and retention in vivo. The quantitative 124I-mIBG PET/CT is a promising new tool to predict tumor radiation doses with 131I-mIBG therapy of neuroblastoma. This methodology may be applied to tumor dosimetry of 131I-mIBG therapy in human subjects using 124I-mIBG pretherapy PET/CT data.

Technical Note: Simplified and practical pretherapy tumor dosimetry — A feasibility study for 131I‐MIBG therapy of neuroblastoma using 124I‐MIBG PET/CT

“…Radiation dose calculated on tumors for radiopharmaceutical therapy (RPT) (i.e., tumor dosimetry) varies significantly from tumor to tumor and from patient to patient . Estimation of radiation dose for both normal tissues and tumors require multiple time point measurements, most often using radionuclide imaging modalities such as single photon emission computed tomography (SPECT) or positron emission tomography (PET).…”

68Ga-DOTATOC and FDG PET Imaging of Preclinical Neuroblastoma Models

“…The ability of animal tumour models of NB to take up PET tracers has been reported with FDG in spontaneous murine NB (12,13). Other studies compared FDG with another metabolic tracer 3'[ 18 F]-fluorothymidine in nude mice grafted with NB cell lines (14,15) or used MIBG labelled with 124 I, a PET radionuclide (16).…”

Preclinical Pharmacokinetics and Dosimetry Studies of 124I/131I-CLR1404 for Treatment of Pediatric Solid Tumors in Murine Xenograft Models

“…Under 2% isoflurane anesthesia in oxygen, the mice were imaged on an Inveon small-animal PET/CT scanner (Siemens). CLR 124 scans were acquired at 1-4, 24, 48, and 72 h after injection, with additional scans at 96, 120, 144, or 168 h. Mice administered 124 I-MIBG were scanned at 1, 4, 24, 48, and 72 h after injection to account for relatively faster biologic clearance observed in similar studies (8,27). During the uptake period before the first scan, the mice were kept conscious in room air.…”