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 (131)I meta-iodobenzylguanidine ((131)I-MIBG) to (90)Y DOTA Phe1-Tyr3-octreotide ((90)Y-DOTATOC) in patients with advanced stage midgut NETs. METHODS: Ten patients were imaged simultaneously with (131)I-MIBG and (111)In-pentetreotide (as a surrogate for (90)Y-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 (131)I-MIBG that could be added to (90)Y-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 (131)I-MIBG could be safely added to (90)Y-DOTATOC (delivered over multiple cycles) by reducing the maximum total deliverable (90)Y-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 (131)I-MIBG to (90)Y-DOTATOC.