Pre-therapeutic dosimetry and biodistribution of 86Y-DOTA-Phe1-Tyr3-octreotide versus 111In-pentetreotide in patients with advanced neuroendocrine tumours

For the internal radiotherapy of neuroendocrine tumours, the somatostatin analogue DOTATOC labelled with Y-90 is frequently used [Y-90-DOTA-Phe(1)-Tyr(3)-octreotide (SMT487-OctreoTher)]. Radiation exposure to the kidneys is critical in this therapy as it may result in renal failure. The aim of this study was to compare cumulative organ and tumour doses based upon dosimetric data acquired with the chemically identical Y-86-DOTA-Phe(1)-Tyr(3)-octreotide (considered as the gold standard) and the commercially available In-111-pentetreotide. Methhods: The cumulative organ and tumour doses for the therapeutic administration of 13.32 GBq Y-90-DOTA-Phe(1)-Tyr(3)-octreotide (three cycles, each of 4.44 GBq) were estimated based on the MIRD concept (MIRDOSE 3.1 and IMEDOSE). Patients with a cumulative kidney dose exceeding 27 Gy had to be excluded from subsequent therapy with Y-90-DOTA-Phe(1)-Tyr(3)-octreotide, in accordance with the directives of the German radiation protection authorities. Results: The range of doses (mGy/MBq Y-90-DOTA-Phe(1)-Tyr(3)-octreotide) for kidneys, spleen, liver and tumour masses was 0.6-2.8, 1.54.2, 0.3-Co1.3 and 2.129.5 (Y-86-DOTA-Phe(1)-Tyr(3)-octreotide), respectively, versus 1.3-3.0, 1.8-Co4.4, 0.2-0.8 and 1.4-19.7 (In-111-pentetreotide), with wide inter-subject variability. Despite renal protection with amino acid infusions, estimated cumulative kidney doses in two patients exceeded 27 Gy. Conclusion: Compared with Y-86-DOTA-Phe(1)-Tyr(3)-octreotide, dosimetry with In-111-pentetreotide overestimated doses to kidneys and spleen, whereas the radiation dose to the tumour-free liver was underestimated. However, both dosimetric approaches detected the two patients with an exceptionally high radiation burden to the kidneys that carried a potential risk of renal failure following radionuclide therapy.