title: Human Anti-Oxidation Protein A1M--A Potential Kidney Protection Agent in Peptide Receptor Radionuclide Therapy.
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.
authors.affiliation: Section for Infection Medicine, Department of Clinical Sciences in Lund, Lund University, Lund 221 84, Sweden. jonas.ahlstedt@med.lu.se.
authors.forename: Jonas
authors.initials: J
authors.lastname: Ahlstedt
authors.affiliation: Lund University Bioimaging Center, Lund University, Lund 221 84, Sweden. thuy.tran@med.lu.se.
authors.forename: Thuy A
authors.initials: TA
authors.lastname: Tran
authors.affiliation: Section of Medical Radiation Physics, Department of Clinical Sciences in Lund, Lund University, Lund 221 84, Sweden. sven-erik.strand@med.lu.se.
authors.forename: Sven-Erik
authors.initials: SE
authors.lastname: Strand
authors.affiliation: Section for Infection Medicine, Department of Clinical Sciences in Lund, Lund University, Lund 221 84, Sweden. magnus.gram@med.lu.se.
authors.forename: Magnus
authors.initials: M
authors.lastname: Gram
authors.affiliation: Section for Infection Medicine, Department of Clinical Sciences in Lund, Lund University, Lund 221 84, Sweden. bo.akerstrom@med.lu.se.
authors.forename: Bo
authors.initials: B
authors.lastname: Åkerström
mesh_terms: D000510:Alpha-Globulins / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000000981:diagnostic imaging* / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D020011:Protective Agents / Q000378:metabolism*; D011874:Radiometry; D011877:Radionuclide Imaging; D018000:Receptors, Peptide / Q000378:metabolism*
chemical_list: D000510:Alpha-Globulins; D020011:Protective Agents; D018000:Receptors, Peptide; C016001:alpha-1-microglobulin
keywords: A1M; PRRT; antioxidation; glomerulus; kidney; octreotide; oxidative stress; radioprotection; tubule