Addition of <sup>131</sup>I-MIBG to PRRT (<sup>90</sup>Y-DOTATOC) for Personalized Treatment of Selected Patients with Neuroendocrine Tumors
David Bushnell, Kellie L. Bodeker, Thomas M. O’Dorisio, Mark T. Madsen, Yusuf Menda, Stephen A. Graves, Gideon Zamba, M. Sue O’Dorisio
Abstract
Peptide receptor radionuclide therapy (PRRT) is an effective treatment for metastatic neuroendocrine tumors. Delivering a sufficient tumor radiation dose remains challenging because of critical-organ dose limitations. Adding 131 I-metaiodobenzylguanidine ( 131 I-MIBG) to PRRT may be advantageous in this regard. Methods: A phase 1 clinical trial was initiated for patients with nonoperable progressive neuroendocrine tumors using a combination of 90 Y-DOTATOC plus 131 I-MIBG. Treatment cohorts were defined by radiation dose limits to the kidneys and the bone marrow. Subject-specific dosimetry was used to determine the administered activity levels. Results: The first cohort treated subjects to a dose limit of 1,900 cGy to the kidneys and 150 cGy to the marrow. No dose-limiting toxicities were observed. Tumor dosimetry estimates demonstrated an expected dose increase of 34%-83% using combination therapy as opposed to 90 Y-DOTATOC PRRT alone. Conclusion: These findings demonstrate the feasibility of using organ dose for a phase 1 escalation design and suggest the safety of using 90 Y-DOTATOC and 131 I-MIBG.