Peptide receptor radionuclide therapy: a new era of radiation nephropathy.

This review article focuses on renal safety in peptide receptor radionuclide therapy (PRRT), particularly in neuroendocrine tumors and other malignancies treated with targeted radionuclide–peptide complexes.

Key points:

• Clinical context: PRRT has improved outcomes by delivering radiation directly to tumor cells while limiting systemic exposure. However, kidneys receive substantial off-target radiation, making radiation nephropathy a major dose-limiting toxicity.

• Mechanisms of kidney injury: The article outlines how the physical and biological properties of different radionuclides (and their decay characteristics) and the peptides used influence renal handling and retention. It summarizes how tubular reabsorption and cortical retention of these agents lead to cumulative radiation injury, with characteristic dose thresholds and pathologic changes of PRRT-induced nephropathy.

• Risk modulation by agent characteristics: The review emphasizes that renal risk varies with the radionuclide–peptide combination, based on their binding, internalization, and clearance profiles.

• Prevention and mitigation strategies:

• Current approaches: primarily amino acid infusions to competitively inhibit proximal tubular reuptake and reduce renal radiation dose; strategies like receptor saturation are also described.
• Emerging approaches: use of cleavable linkers and potential nephroprotective agents aimed at further limiting renal radiation exposure.

• Special populations: The authors address how to approach PRRT in patients with pre-existing chronic kidney disease and in those receiving dialysis, including altered pharmacokinetics and the need for individualized dosing and timing.

• Practice implications: The review calls for close collaboration between oncologists, nuclear medicine physicians, and nephrologists to balance oncologic efficacy with renal safety as PRRT indications expand.