Nephrotoxicity after PRRT with (177)Lu-DOTA-octreotate

Area of Science:

• Nuclear Medicine
• Oncology
• Nephrology

Background:

• Peptide receptor radionuclide therapy (PRRT) using somatostatin analogues is a key treatment for neuroendocrine tumors.
• Renal toxicity is a known complication, particularly with 90Y-labeled analogues, with risk factors like hypertension and diabetes identified.
• The safety profile of 177Lu-labeled analogues, specifically [177Lu-DOTA0,Tyr3]-Octreotate, regarding renal function requires further investigation.

Purpose of the Study:

• To evaluate renal function over time in patients undergoing [177Lu-DOTA0,Tyr3]-Octreotate therapy.
• To determine the incidence of nephrotoxicity and identify associated risk factors.
• To compare absorbed kidney radiation doses with established limits for external beam radiotherapy and 90Y-PRRT.

Main Methods:

• Assessed annual decrease in creatinine clearance (CLR) in 209 patients.
• Evaluated the incidence of grade 3 or 4 renal toxicity in 323 patients using CTCAE v4.03 criteria.
• Utilized nonlinear mixed-effects modeling to analyze risk factors and calculated kidney radiation doses for association with renal function decline.

Main Results:

• Only 3% of patients (n=323) experienced subacute grade 2 renal toxicity; no grade 3 or 4 nephrotoxicity was observed.
• The mean annual decrease in CLR was 3.4%, with no patient showing a decrease >20%.
• No baseline risk factors (hypertension, diabetes, cumulative activity, kidney dose) significantly impacted renal function over time. Mean kidney dose was 20.1 Gy.

Conclusions:

• Treatment with [177Lu-DOTA0,Tyr3]-Octreotate is associated with low incidence of nephrotoxicity.
• Identified risk factors for renal toxicity were not significant in this patient cohort.
• The study suggests that radiation dose thresholds established for external beam radiotherapy and 90Y-PRRT may not be directly applicable to 177Lu-PRRT.