Feasibility and advantage of adding I-131-MIBG to Y-90-DOTATOC for treatment of patients with advanced stage neuroendocrine tumors

• Type of Material: Article
• Authors: David L. Bushnell, University of Iowa; Mark T. Madsen, University of Iowa; Thomas O'cdorisio, University of Iowa; Yusuf Menda, University of Iowa; Saima Muzahir, Emory University; Randi Ryan, University of Iowa; M. Sue O'dorisio, University of Iowa
• Language: English
• Date: 2014-09-10
• Publisher: BMC (part of Springer Nature)
• Publication Version: Final Published Version
• Copyright Statement: © 2014, Bushnell et al.; licensee Springer.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s13550-014-0038-2
• Title of Journal or Parent Work: EJNMMI Research
• ISSN: 2191-219X
• Volume: 4
• Issue: 1
• Start Page: 38
• End Page: 38
• Grant/Funding Information: This project was supported by a Veterans Administration Merit Review Grant (Bushnell PI).
• Keywords: Neuroendocrine tumors; METAIODOBENZYLGUANIDINE; CARCINOID-TUMORS; Life Sciences & Biomedicine; Radionuclide theranostics; RECEPTOR RADIONUCLIDE THERAPY; I-131-MIBG; DOSIMETRY; Radiology, Nuclear Medicine & Medical Imaging; BIODISTRIBUTION; I-131-METAIODOBENZYLGUANIDINE; Science & Technology; SURVIVAL; RADIOPEPTIDE THERAPY; RENAL TOXICITY; RADIOLABELED SOMATOSTATIN ANALOG; Y-90-DOTATOC
• Research Categories: Health Sciences, Radiology; Health Sciences, Oncology

Abstract

Background: Peptide receptor radionuclide therapy (PRRT) is an effective form of treatment for patients with metastatic neuroendocrine tumors (NETs). However, delivering sufficient radiation dose to the tumor to result in a high percentage of long-term tumor remissions remains challenging because of the limits imposed on administered activity levels by radiation damage to normal tissues. The goal of this study was to evaluate the dosimetric advantages of adding 131I meta-iodobenzylguanidine (131I-MIBG) to 90Y DOTA Phe1-Tyr3-octreotide (90Y-DOTATOC) in patients with advanced stage midgut NETs. Methods: Ten patients were imaged simultaneously with 131I-MIBG and 111In-pentetreotide (as a surrogate for 90Y-DOTATOC) on days 1, 2, and 3 post-administration. Blood samples were obtained at the same time points. Using dosimetry measures from this data and our previously published methodology for calculating optimal combined administered activity levels for therapy, we determined the amount of 131I-MIBG that could be added to 90Y-DOTATOC without exceeding normal organ dose limits (marrow and kidneys) along with the expected increase in associated tumor dose, if any. Results: We found that a median value of 34.6 GBq of 131I-MIBG could be safely added to 90Y-DOTATOC (delivered over multiple cycles) by reducing the maximum total deliverable 90Y-DOTATOC by a median value of 24.5%. Taking this treatment approach, we found that there would be a median increase in deliverable tumor dose of 4,046 cGy in six of the ten subjects. Of note, there were a small number of metastases that were positive for only one or the other of these radiopharmaceuticals within the same subject. Conclusions: We conclude that approximately half of the patients with midgut NETs that are eligible for PRRT could reasonably be expected to benefit from the addition of 131I-MIBG to 90Y-DOTATOC.