Recombinant α 1 -Microglobulin Is a Potential Kidney Protector in 177 Lu-Octreotate Treatment of Neuroendocrine Tumors.

Treatment of neuroendocrine tumors with ¹⁷⁷ Lu-octreotate results in prolonged survival and improved quality of life for the patient. However, the treatment is today limited by side effects on kidney and bone marrow, and complete tumor remission is rarely seen. A possible way to minimize dose-limiting toxicity and to optimize this treatment method is to use radioprotectors in conjunction with radiotherapy. A recombinant form of α ₁ -microglobulin (rA1M) was recently shown to preserve kidney structure and function after ¹⁷⁷ Lu-octreotate injection in mice and was suggested as a radioprotector in peptide receptor radionuclide therapy. The aims of this work were to investigate the influence of rA1M on the in vivo biokinetics of ¹⁷⁷ Lu-octreotate, with a focus on tumor tissue, and to study the impact of rA1M on the therapeutic response in tumor tissue subjected to ¹⁷⁷ Lu-octreotate treatment. Methods: The biodistribution of ¹⁷⁷ Lu-octreotate was examined in BALB/c nude mice with GOT2 tumors 1-168 h after injection with either ¹⁷⁷ Lu-octreotate or coadministration of ¹⁷⁷ Lu-octreotate and rA1M. The effects of rA1M on the tumor response after ¹⁷⁷ Lu-octreotate treatment were studied in BALB/c nude mice with GOT1 tumors. Three groups of mice were administered rA1M, ¹⁷⁷ Lu-octreotate, or both. Another group served as untreated controls. Tumor volume was measured to follow the treatment effects. Results: No statistically significant difference in biodistribution of ¹⁷⁷ Lu was observed between the groups receiving ¹⁷⁷ Lu-octreotate or coinjection of ¹⁷⁷ Lu-octreotate and rA1M. The therapy study showed a decrease in mean tumor volume during the first 2 wk for both the ¹⁷⁷ Lu-octreotate group and the coadministration group, followed by tumor regrowth. No statistically significant difference between the groups was found. Conclusion: rA1M did not negatively impact absorbed dose to tumor or therapeutic response in combination with ¹⁷⁷ Lu-octreotate and may be a promising kidney protector during ¹⁷⁷ Lu-octreotate treatment of patients with neuroendocrine tumors.
(© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)