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.
Highlights
Neuroendocrine tumors (NETs) are a large group of neoplasms derived from the neuroendocrine system
A majority of NETs has a strong over-expression of somatostatin receptors, mainly subtype 2, which is the key target for therapy using stable somatostatin analogues (SSA) [3]
111In-octreotide infusion to this day remains a therapeutic option for NETs, it has been replaced by conjugates with β-emitters such as 90Y and 177Lu
Summary
Neuroendocrine tumors (NETs) are a large group of neoplasms derived from the neuroendocrine system. Peptide receptor radionuclide therapy (PRRT) using somatostatin analogues such as octreotide chelated to β-emitting radionuclides (177Lu, 90Y) have been successfully used to target inoperable or metastatic NETs for the past 15 years. PRRT utilizing the two radiopharmaceuticals 90Y-[DOTA0, Tyr3]-octreotide (DOTATOC) and 177Lu-[DOTA0, Tyr3]-octreotate (DOTATATE) has proven to be an effective and safe alternative treatment for patients with metastatic NETs [6,7] Both peptides are derivatized somatostatin analogues that show high affinity for sstr. A recent large international multi-center trial [11] has shown marked improvement in progression-free survival rate and overall survival in patients undergoing PRRT with DOTATATE
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