Recombinant alpha(1)-Microglobulin Is a Potential Kidney Protector in Lu-177-Octreotate Treatment of Neuroendocrine Tumors

• Treatment of neuroendocrine tumors with Lu-177-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 alpha(1)-microglobulin ( rA1M) was recently shown to preserve kidney structure and function after Lu-177-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 Lu-177-octreotate, with a focus on tumor tissue, and to study the impact of rA1M on the therapeutic response in tumor tissue subjected to Lu-177-octreotate treatment. Methods: The biodistribution of Lu-177-octreotate was examined in BALB/c nude mice with GOT2 tumors 1-168 h after injection with either Lu-177-octreotate or coadministration of 177Lu-octreotate and rA1M. The effects of rA1M on the tumor response after Lu-177-octreotate treatment were studied in BALB/c nude mice with GOT1 tumors. Three groups of mice were administered rA1M, Lu-177-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 Lu-177 was observed between the groups receiving Lu-177-octreotate or coinjection of Lu-177-octreotate and rA1M. The therapy study showed a decrease in mean tumor volume during the first 2 wk for both the Lu-177-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 Lu-177-octreotate and may be a promising kidney protector during Lu-177-octreotate treatment of patients with neuroendocrine tumors.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

alpha(1)-microglobulin

somatostatin receptors

GOT1

GOT2

radioprotector

medullary-thyroid carcinoma

radionuclide therapy

lipocalin

alpha(1)-microglobulin

radiolabeled somatostatin

nude-mice

biodistribution

toxicity

model

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)