TY - JOUR
T1 - Recombinant A1-microglobulin is a potential kidney protector in 177Lu-octreotate treatment of neuroendocrine tumors
AU - Andersson, Charlotte K.
AU - Shubbar, Emman
AU - Schüler, Emil
AU - Kerström, Bo
AU - Gram, Magnus
AU - Forssell-Aronsson, Eva B.
N1 - Funding Information:
This study was supported by the Swedish Research Council (grants 21073 and 00696), the Swedish Cancer Society (grant 3427), BioCARE (a National Strategic Research Program at the University of Gothenburg), the Swedish state under an agreement between the Swedish government and the county councils (the ALF-agreement; ALFGBG-725031), the King Gustav V Jubilee Clinic Cancer Research Foundation, Sahlgrenska University Hospital Research Funds, the Wilhelm and Martina Lundgren Research Foundation, the Assar Gabrielsson Cancer Research Foundation, and the Herbert & Karin Jacobsson Foundation. Magnus Gram and Bo Åkerström are cofounders and shareholders of A1M Pharma AB, which holds patents related to A1M use and production. No other potential conflict of interest relevant to this article was reported.
Publisher Copyright:
COPYRIGHT © 2019 by the Society of Nuclear Medicine and Molecular Imaging.
PY - 2019
Y1 - 2019
N2 - Treatment of neuroendocrine tumors with 177Lu-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 α1-microglobulin (rA1M) was recently shown to preserve kidney structure and function after 177Lu-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 177Lu-octreotate, with a focus on tumor tissue, and to study the impact of rA1M on the therapeutic response in tumor tissue subjected to 177Lu-octreotate treatment. Methods: The biodistribution of 177Lu-octreotate was examined in BALB/c nude mice with GOT2 tumors 1–168 h after injection with either 177Lu-octreo-tate or coadministration of 177Lu-octreotate and rA1M. The effects of rA1M on the tumor response after 177Lu-octreotate treatment were studied in BALB/c nude mice with GOT1 tumors. Three groups of mice were administered rA1M, 177Lu-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 177Lu was observed between the groups receiving 177Lu-octreotate or coinjection of 177Lu-octreotate and rA1M. The therapy study showed a decrease in mean tumor volume during the first 2 wk for both the 177Lu-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 177Lu-octreotate and may be a promising kidney protector during 177Lu-octreotate treatment of patients with neuroendocrine tumors.
AB - Treatment of neuroendocrine tumors with 177Lu-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 α1-microglobulin (rA1M) was recently shown to preserve kidney structure and function after 177Lu-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 177Lu-octreotate, with a focus on tumor tissue, and to study the impact of rA1M on the therapeutic response in tumor tissue subjected to 177Lu-octreotate treatment. Methods: The biodistribution of 177Lu-octreotate was examined in BALB/c nude mice with GOT2 tumors 1–168 h after injection with either 177Lu-octreo-tate or coadministration of 177Lu-octreotate and rA1M. The effects of rA1M on the tumor response after 177Lu-octreotate treatment were studied in BALB/c nude mice with GOT1 tumors. Three groups of mice were administered rA1M, 177Lu-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 177Lu was observed between the groups receiving 177Lu-octreotate or coinjection of 177Lu-octreotate and rA1M. The therapy study showed a decrease in mean tumor volume during the first 2 wk for both the 177Lu-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 177Lu-octreotate and may be a promising kidney protector during 177Lu-octreotate treatment of patients with neuroendocrine tumors.
KW - GOT1
KW - GOT2
KW - Radioprotector
KW - Somatostatin receptors
KW - α-microglobulin
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U2 - 10.2967/jnumed.118.225243
DO - 10.2967/jnumed.118.225243
M3 - Article
C2 - 30926650
AN - SCOPUS:85074379101
SN - 0161-5505
VL - 60
SP - 1600
EP - 1604
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 11
ER -