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Review
. 2015 Dec 18;16(12):30309-20.
doi: 10.3390/ijms161226234.

Human Anti-Oxidation Protein A1M--A Potential Kidney Protection Agent in Peptide Receptor Radionuclide Therapy

Jonas Ahlstedt  1 , Thuy A Tran  2 , Sven-Erik Strand  3 , Magnus Gram  4 , Bo Åkerström  5
Affiliations
Review

Human Anti-Oxidation Protein A1M--A Potential Kidney Protection Agent in Peptide Receptor Radionuclide Therapy

Jonas Ahlstedt et al. Int J Mol Sci. .

Abstract

Peptide receptor radionuclide therapy (PRRT) has been in clinical use for 15 years to treat metastatic neuroendocrine tumors. PRRT is limited by reabsorption and retention of the administered radiolabeled somatostatin analogues in the proximal tubule. Consequently, it is essential to develop and employ methods to protect the kidneys during PRRT. Today, infusion of positively charged amino acids is the standard method of kidney protection. Other methods, such as administration of amifostine, are still under evaluation and show promising results. α₁-microglobulin (A1M) is a reductase and radical scavenging protein ubiquitously present in plasma and extravascular tissue. Human A1M has antioxidation properties and has been shown to prevent radiation-induced in vitro cell damage and protect non-irradiated surrounding cells. It has recently been shown in mice that exogenously infused A1M and the somatostatin analogue octreotide are co-localized in proximal tubules of the kidney after intravenous infusion. In this review we describe the current situation of kidney protection during PRRT, discuss the necessity and implications of more precise dosimetry and present A1M as a new, potential candidate for renal protection during PRRT and related targeted radionuclide therapies.

Keywords: A1M; PRRT; antioxidation; glomerulus; kidney; octreotide; oxidative stress; radioprotection; tubule.

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Figures

Figure 1
Figure 1
Visualizing the distribution of 125I-labelled A1M 20 minutes post-injection at different magnification using SPECT/CT (A) and digital autoradiography (B) at the organ-level and fluorescence imaging showing both A1M (green), octreotide (red) and cell nuclei (blue) (C,D) at cellular and sub-cellular levels. The arrow in (D) indicates one single cell. The figure is modified from reference 35 with permission from the publisher.
Figure 2
Figure 2
Three-dimensional rendering of A1M based on the published crystal structure [51]. The position of the C34 group (mutated to serine in the crystal structure) is highlighted in red. This is the critical site for the reductase, heme binding, and radical scavenging properties of A1M.
See this image and copyright information in PMC

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