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

• Published in: Molecular imaging and biology Vol. 14; no. 6; pp. 735 - 742
• Main Authors: Seo, Youngho, Gustafson, W. Clay, Dannoon, Shorouk F., Nekritz, Erin A., Lee, Chang-Lae, Murphy, Stephanie T., VanBrocklin, Henry F., Hernandez-Pampaloni, Miguel, Haas-Kogan, Daphne A., Weiss, William A., Matthay, Katherine K.
• Format: Journal Article
• Language: English
• Published: New York Springer-Verlag 01.12.2012; Springer Nature B.V
• Subjects: 3-Iodobenzylguanidine - pharmacokinetics; 3-Iodobenzylguanidine - therapeutic use; Animal models; Animals; Disease Models, Animal; Humans; Imaging; Imaging, Three-Dimensional; Iodine Radioisotopes; Medicine; Medicine & Public Health; Mice; Mice, Nude; Neuroblastoma - diagnostic imaging; Neuroblastoma - drug therapy; Norepinephrine Plasma Membrane Transport Proteins - metabolism; Organ Specificity; Positron-Emission Tomography; Radiation Dosage; Radiology; Research Article; X-Ray Microtomography; Xenograft Model Antitumor Assays; Animal model; M-iodobenzylguanidine; Iodine-124; PET/CT; Radiation dosimetry; Neuroblastoma; Iodine-131
• ISSN: 1536-1632; 1860-2002; 1860-2002
• DOI: 10.1007/s11307-012-0552-4

Purpose [ 124 I]m-iodobenzylguanidine ( 124 I-mIBG) provides a quantitative tool for pretherapy tumor imaging and dosimetry when performed before [ 131 I]m-iodobenzylguanidine ( 131 I-mIBG) targeted radionuclide therapy of neuroblastoma. 124 I ( T 1/2  = 4.2 days) has a comparable half-life to that of 131 I ( 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 131 I-mIBG therapy using 124 I-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. 124 I-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 124 I-mIBG. Dose estimates for 131 I-mIBG were made, assuming the same in vivo biodistribution as 124 I-mIBG. Results All NB1691-hNET tumors had significant uptake and retention of 124 I-mIBG, whereas unmodified NB1691 tumors did not demonstrate quantifiable mIBG uptake in vivo , despite in vitro uptake. 124 I-mIBG with microPET/CT provided an accurate three-dimensional tool for estimating the radiation dose that would be delivered with 131 I-mIBG therapy. For example, in our model system, we estimated that the administration of 131 I-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 124 I-mIBG uptake and retention in vivo . The quantitative 124 I-mIBG PET/CT is a promising new tool to predict tumor radiation doses with 131 I-mIBG therapy of neuroblastoma. This methodology may be applied to tumor dosimetry of 131 I-mIBG therapy in human subjects using 124 I-mIBG pretherapy PET/CT data.