Abstract
BackgroundLu-[DOTA0, Tyr3]-octreotate (177Lu-octreotate) is used to treat neuroendocrine tumors with high somatostatin-receptor expression. 177Lu-octreotate is mainly excreted via the kidneys, but to some extent, accumulates in the kidney cortex due to, e.g., tubular reabsorption. Renal toxicity is one of the main limiting factors in 177Lu-octreotate treatment. Further knowledge of the biodistribution and dosimetry of 177Lu-octreotate in individual patients is needed. The aim of this study was to estimate the absorbed dose to the kidneys and compare the results obtained with planar imaging and different dosimetric methods: (1) conjugate-view (CV) method using patient-specific kidney sizes, (2) PA method, based on posterior images only, (3) CV method with reduced number of time points (CVreduced data), and (4) CV method using standard kidney sizes (CVstandard size).MethodsTotally, 33 patients each received 3.4 to 8.2 GBq of 177Lu-octreotate up to five times, with infusion of lysine and arginine to block the renal uptake. Whole-body planar gamma camera images were acquired on days 0, 1, 2, and 7. The 177Lu concentration in the kidneys was determined by the CV method, and the absorbed dose was estimated with patient-specific organ sizes. Comparison to the CV method was made using posterior images only, together with the influence of the number of time points and with standard organ sizes.ResultsLarge interindividual variations were found in the time-activity curve pattern and in the absorbed dose to the kidneys using the CV method: 0.33 to 2.4 Gy/GBq (mean = 0.80 Gy/GBq, SD = 0.30). In the individual patient, the mean deviation of all subsequent kidney doses compared to that of the first administration was 1% (SD = 19%) and 5% (SD = 23%) for the right and left kidneys, respectively. Excluding data for day 7 resulted in large variations in the absorbed dose.ConclusionLarge interindividual variations in kidney dose were found, demonstrating the need for patient-specific dosimetry and treatment planning.
Highlights
Lu-[DOTA0, Tyr3]-octreotate (177Lu-octreotate) is used to treat neuroendocrine tumors with high somatostatin-receptor expression. 177Lu-octreotate is mainly excreted via the kidneys, but to some extent, accumulates in the kidney cortex due to, e.g., tubular reabsorption
The present study focused on D/Aadministered to kidneys in patients with neuroendocrine tumors after fractionated treatment with 177Lu-octreotate
The importance of patientspecific kidney and body sizes was demonstrated for kidney dose estimation of 177Lu-octreotate
Summary
Lu-[DOTA0, Tyr3]-octreotate (177Lu-octreotate) is used to treat neuroendocrine tumors with high somatostatin-receptor expression. 177Lu-octreotate is mainly excreted via the kidneys, but to some extent, accumulates in the kidney cortex due to, e.g., tubular reabsorption. After infusion of 177Lu-octreotate, 177Lu is mainly excreted via the kidneys and reabsorbed and accumulated in the kidney cortex [5,6,7,8,9,10] The mechanisms behind this accumulation are not fully understood, but studies on rats indicate that endocytosis either via the megalincubulin complex, or via ligand-specific endocytosis, pinocytosis, organic anion and cation transporters families, and oligopeptide transporters, are involved [5,8,10,11,12,13]. To avoid adverse effects of 177Lu-octreotate and to determine the tolerance dose to kidneys, there is a need for better knowledge of the renal biodistribution, biokinetics, and dosimetry of 177Lu-octreotate and of relevant radiobiological and toxicity factors [4,5,11]
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