Abstract
α1-Microglobulin (A1M) is an antioxidant found in all vertebrates, including humans. It has enzymatic reductase activity and can scavenge radicals and bind free heme groups. Infused recombinant A1M accumulates in the kidneys and has therefore been successful in protecting kidney injuries in different animal models. In this review, we focus on A1M as a radioprotector of the kidneys during peptide receptor radionuclide/radioligand therapy (PRRT/RLT). Patients with, e.g., neuroendocrine tumors or castration resistant prostate cancer can be treated by administration of radiolabeled small molecules which target and therefore enable the irradiation and killing of cancer cells through specific receptor interaction. The treatment is not curative, and kidney toxicity has been reported as a side effect since the small, radiolabeled substances are retained and excreted through the kidneys. In recent studies, A1M was shown to have radioprotective effects on cell cultures as well as having a similar biodistribution as the somatostatin analogue peptide 177Lu-DOTATATE after intravenous infusion in mice. Therefore, several animal studies were conducted to investigate the in vivo radioprotective potential of A1M towards kidneys. The results of these studies demonstrated that A1M co-infusion yielded protection against kidney toxicity and improved overall survival in mouse models. Moreover, two different mouse studies reported that A1M did not interfere with tumor treatment itself. Here, we give an overview of radionuclide therapy, the A1M physiology and the results from the radioprotector studies of the protein.
Highlights
Acute kidney injury (AKI) can occur in conjunction with a wide array of diseases and medical conditions inducing various forms of stress to this organ [1]
In vivo animal models have been employed to show pre-clinical therapeutic properties in preeclampsia, a pregnancy complication characterized by hemolysis, hypertension and AKI [113], peptide receptor radionuclide therapy (PRRT), i.e., tumor radiotherapy associated with AKI, and intraventricular hemorrhage of prematurely born babies (IVH) which is associated with hemolysis, inflammation and subsequent brain damage [114]
Results suggest that administration of A1M as treatment during PRRT and radioligand therapy (RLT) should be given at the same time or slightly later
Summary
Acute kidney injury (AKI) can occur in conjunction with a wide array of diseases and medical conditions inducing various forms of stress to this organ [1]. The mediators of oxidative stress include free radicals and reactive oxygen species (ROS). These are produced in cells and tissues in normal biological processes, such. The impact of radiation-based cancer therapy modalities, peptide receptor radionuclide therapy (PRRT) and radioligand therapy (RLT), on kidney function will be discussed. In both of these, infused radiolabeled small molecules target metastatic tumors through specific receptor interaction, resulting in killing of the tumor cells by irradiation damage [10]. The use of A1M as a renal protector will be discussed in the light of recent promising results in in vivo mouse models
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