Division of Nuclear Medicine, Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City, IA.
Division of Nuclear Medicine, Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City, IA.
Semin Nucl Med. 2022 Jul;52(4):467-474. doi: 10.1053/j.semnuclmed.2022.02.004. Epub 2022 Mar 18.
Radiopharmaceuticals used for cancer therapy are highly selective, designed to kill malignant cells and spare healthy tissues. Side effect rates are generally less than other treatments, but it is still the utmost concern to minimize normal organ toxicity and maximize radiation dose to the target lesions in applying radiopharmaceutical therapies (RPTs). Most commonly affected normal organs include bone marrow, kidneys and liver. The impact of RPTs to renal function is generally considered low. Peptide receptor radionuclide therapy (PRRT) using somatostatin radiopharmaceuticals, particularly Y-DOTATOC, has the potential to induce nephrotoxicity. This is because PRRT radiopharmaceuticals are primarily cleared thorough glomerular filtration and reabsorption/retainment of them at the renal proximal tubules exposes kidneys to additional radiation. Amino acid co-infusion is the standard regimen for competitive inhibition of tubular reabsorption of PRRT radiopharmaceuticals to mitigate nephrotoxicity. Other measures to protect renal function include hydration, use of plasma expander or radioprotectant, personalized renal dosimetry to limit renal radiation dose and close monitoring of renal function. Limited data suggest alpha emitter PRRT radiopharmaceuticals have less impact on kidney function compared to beta emitter PRRT, but more studies are needed for long term renal toxicity. I-MIBG is primarily excreted unchanged thorough the kidneys but renal absorbed dose is low and potential toxicities to the bone marrow and lungs are the most significant clinical concerns. Other RPTs that are not mainly cleared through kidneys such as Ra or radioimmunotherapy have no concern for kidney toxicity.
用于癌症治疗的放射性药物具有高度的选择性,旨在杀死恶性细胞而不伤害健康组织。副作用发生率通常低于其他治疗方法,但在应用放射性药物治疗(RPTs)时,仍然需要最大限度地减少正常器官毒性并最大限度地提高靶病变的辐射剂量,这是最需要关注的问题。最常受影响的正常器官包括骨髓、肾脏和肝脏。RPT 对肾功能的影响通常被认为较低。使用生长抑素放射性药物的肽受体放射性核素治疗(PRRT),特别是 Y-DOTATOC,有可能引起肾毒性。这是因为 PRRT 放射性药物主要通过肾小球滤过清除,而它们在肾近端小管的重吸收/保留会使肾脏暴露于额外的辐射下。氨基酸共输注是竞争抑制 PRRT 放射性药物肾小管重吸收以减轻肾毒性的标准方案。保护肾功能的其他措施包括水化、使用血浆扩容剂或放射保护剂、个性化肾脏剂量学以限制肾脏辐射剂量以及密切监测肾功能。有限的数据表明,与β发射体 PRRT 相比,α发射体 PRRT 放射性药物对肾功能的影响较小,但需要更多的长期肾毒性研究。I-MIBG 主要通过肾脏不变地排泄,但肾脏吸收剂量较低,骨髓和肺部的潜在毒性是最显著的临床关注点。其他主要不通过肾脏清除的 RPT,如 Ra 或放射免疫疗法,对肾脏毒性没有影响。