Addition of 131I-MIBG to PRRT (90Y-DOTATOC) for Personalized Treatment of Selected Patients with Neuroendocrine Tumors

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 ¹³¹I-metaiodobenzylguanidine (¹³¹I-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 ⁹⁰Y-DOTATOC plus ¹³¹I-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 ⁹⁰Y-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 ⁹⁰Y-DOTATOC and ¹³¹I-MIBG.

Keywords: DOTATOC; MIBG; PRRT; personalized dosimetry.