TY - JOUR T1 - Potential Increased Tumor-Dose Delivery with Combined <sup>131</sup>I-MIBG and <sup>90</sup>Y-DOTATOC Treatment in Neuroendocrine Tumors: A Theoretic Model JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 660 LP - 667 VL - 47 IS - 4 AU - Mark T. Madsen AU - David L. Bushnell AU - Malik E. Juweid AU - Yusuf Menda AU - M. Sue O'Dorisio AU - Thomas O'Dorisio AU - Ian M. Besse Y1 - 2006/04/01 UR - http://jnm.snmjournals.org/content/47/4/660.abstract N2 - 131I-Metaiodobenzylguanidine (MIBG) and 90Y-DOTA-d-Phe1-Tyr3-octreotide (DOTATOC) have been used as radiotherapeutic agents for treating neuroendocrine tumors. The tumor dose delivered by these agents is often insufficient to control or cure the disease. However, these 2 agents used together could potentially increase tumor dose without exceeding the critical organ dose because the dose-limiting tissues are different. In this paper, we investigate the conditions in which combined-agent therapy is advantageous and we quantify the expected tumor-dose gain. Methods: A series of equations was derived that predicted the optimal combination of agents and the fractional increase in tumor dose available from combined-agent therapy with respect to either 131I-MIBG or 90Y-DOTATOC. The results obtained from these derivations were compared with direct dose calculations using published dosimetric organ values for 131I-MIBG and 90Y-DOTATOC along with critical organ-dose limits. Tumor dose was calculated as a function of the tumor-dose ratio, defined as the 90Y-DOTATOC tumor dose per megabecquerel divided by the 131I-MIBG tumor dose per megabecquerel. Comparisons were made between the dose delivered to tumor with single-agent therapy and the dose delivered to tumor with combined-agent therapy as a function of the tumor-dose ratio and the fraction of activity contributed by each agent. Results: The dose model accurately predicted the optimal combination of agents, the range at which combined-agent therapy was advantageous, and the magnitude of the increase. For the published organ dosimetry and critical organ-dose limits, combined-agent therapy increased tumor dose when the tumor-dose ratio was greater than 0.67 and less than 5.93. The maximum combined-agent tumor-dose increase of 68% occurred for a tumor-dose ratio of 2.57, using 92% of the maximum tolerated 90Y-DOTATOC activity supplemented with 76% of the maximum tolerated activity of 131I-MIBG. Variations in organ dose per megabecquerel and dose-limiting values altered both the magnitude of the increase and the range at which combined-agent therapy was advantageous. Conclusion: Combining 131I-MIBG and 90Y-DOTATOC for radiotherapy of neuroendocrine tumors can significantly increase the delivered tumor dose over the dose obtained from using either agent alone. Prior knowledge of the normal-organ and tumor dosimetry of both agents is required to determine the magnitude of the increase. ER -