Renal Toxicity of Radiolabeled Peptides and Antibody Fragments: Mechanisms, Impact on Radionuclide Therapy, and Strategies for Prevention
Open accessAbstract
Peptide-receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs such as octreotide is an effective therapy against neuroendocrine tumors. Other radiolabeled peptides and antibody fragments are under investigation. Most of these compounds are cleared through the kidneys and reabsorbed and partially retained in the proximal tubules, causing dose-limiting nephrotoxicity. An overview of renal handling of radiolabeled peptides and resulting nephrotoxicity is presented, and strategies to reduce nephrotoxicity are discussed. Modification of size, charge, or structure of radiolabeled peptides can alter glomerular filtration and tubular reabsorption. Coinfusion of competitive inhibitors of reabsorption also interferes with the interaction of peptides with renal endocytic receptors; coinfusion of basic amino acids is currently used for kidney protection in clinical PRRT. Furthermore, nephrotoxicity may be reduced by dose fractionation, use of radioprotectors, or use of mitigating agents. Decreasing the risk of nephrotoxicity allows for administration of higher radiation doses, increasing the effectiveness of PRRT.
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To capture the true incidence of renal impairment after RPT, a sufficient follow-up time of at minimum 6-12 months is required.
“Notably, to capture the true incidence of renal impairment after RPT a suf fi cient follow-up time of at minimum 6 -12 mo is required ( 62 ).”
From Normal-Tissue Tolerance to Radiopharmaceutical Therapies, the Knowns and the Unknowns (2021) · cites this paper as [62]
The section on external-beam radiation therapy (p. 5) says acute radiation nephropathy develops within 6–12 months, supporting the need to consider delayed impairment. But the paper does not prescribe 6–12 months as a minimum follow-up after radionuclide therapy to capture its true incidence; it also says chronic nephropathy can develop years later. (LLM, conf=0.85)
Experimental — accuracy not yet measuredHydrophilic radiolabeled peptides such as 177Lu-DOTATATE are mainly filtered by the glomeruli and partly reabsorbed by the proximal tubular cells.
“Hydrophilic radiolabeled peptides such as 177 Lu-DOTATATE are mainly fi ltered by the glomeruli and partly reabsorbed by the proximal tubular cells ( 62 ).”
From Normal-Tissue Tolerance to Radiopharmaceutical Therapies, the Knowns and the Unknowns (2021) · cites this paper as [62]
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- Authors
- Vegt, E., de Jong, M., Wetzels, J. F. M., Masereeuw, R., Melis, M., Oyen, W. J. G., Gotthardt, M., & Boerman, O. C.
- Affiliations
- Radboud University Medical Center (NL)
- Tohoku University (JP)
- Erasmus MC (NL)
- ORCID
- Venue
- Journal of Nuclear Medicine
- Publisher
- Society of Nuclear Medicine
- Published
- 2010-06-16
- Volume
- 51
- Issue
- 7
- Pages
- 1049-1058
- ISSN
- 0161-5505 (ISSN-L)
- 2159-662X
- OpenAlex
- W2135593703
- Cited by
- 334
- References
- 78
- Citations by year
- 2026: 25 · 2025: 33 · 2024: 18 · 2023: 26 · 2022: 23 · 2021: 31 · 2020: 18 · 2019: 15 · 2018: 15 · 2017: 14 · 2016: 21 · 2015: 15 · 2014: 28 · 2013: 17 · 2012: 22
- FWCI
- 2.37
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- Locations
- Journal of Nuclear Medicine (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Health Sciences › Medicine › Epidemiology › Neuroendocrine Tumor Research Advances
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Keywords
- nephrotoxicity, peptide receptor radionuclide therapy, radiolabeled peptides, antibody fragments, somatostatin analogues, octreotide, neuroendocrine tumors, proximal tubular reabsorption, glomerular filtration, basic amino acids, dose fractionation, radioprotective agents, renal protection
- MeSH terms
- Animals, Dose-Response Relationship, Radiation, Humans, Immunoglobulin Fragments, Kidney, Kidney Diseases, Peptides, Radiopharmaceuticals
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