The effect of long-acting somatostatin analogues on the uptake of [177Lu]Lu-HA-DOTATATE.

PURPOSE: According to IAEA/EANM/SNMMI guidelines, long-acting somatostatin analogues (LA-SSAs) should be discontinued 4-6 weeks prior to peptide receptor radionuclide therapy (PRRT) to prevent somatostatin receptor saturation. The aim of this study was to determine the effect of continued use of long-acting SSAs during PRRT on the uptake of [177Lu]Lu-HA-DOTATATE on SPECT/CT. METHODS: Consecutive patients with neuroendocrine tumours who were treated with PRRT receiving 7.4 GBq of [177Lu]Lu-HA-DOTATATE were included. Patients were divided into 3 groups: (1) control (LA-SSA stopped > 6 weeks prior to PRRT), or continued treatment with (2) long-acting octreotide < 6 weeks prior to PRRT, or (3) long-acting lanreotide < 6 weeks prior to PRRT. The uptake of [177Lu]Lu-HA-DOTATATE was quantified in healthy tissues (spleen, liver, kidneys, bone marrow) and tumour lesions on SPECT/CT performed 24 h after PRRT. A Mann-Whitney U test was used to determine differences in uptake between the long-acting octreotide and long-acting lanreotide groups compared to the control group. RESULTS: Forty-two patients with 135 cycles of PRRT were included: 28 with lanreotide, 50 with octreotide, and 57 cycles without LA-SSAs. Uptake of [177Lu]Lu-HA-DOTATATE was significantly decreased in liver parenchyma in patients with lanreotide (p < 0.001) and in the spleen in patients with either octreotide or lanreotide (both p < 0.001). No differences were observed for uptake in kidneys, bone marrow, and blood pool. Uptake of [177Lu]Lu-HA-DOTATATE in tumours was the same in patients with lanreotide compared to the control (p = 0.862) and in patients with octreotide compared to the control (p = 0.201), independent of tumour location. CONCLUSION: Long-acting octreotide and lanreotide do not interfere with the uptake of [177Lu]Lu-HA-DOTATATE in tumour lesions 24 h post-injection. Uptake in healthy liver parenchyma significantly decreases after lanreotide administration prior to PRRT, while uptake in healthy spleen tissue significantly decreases with both octreotide and lanreotide administration.

Somatostatin receptor saturation after administration of high peptide amounts of [177Lu]Lu-HA-DOTATATE: when enough is enough.

BACKGROUND: Receptor saturation during peptide receptor radionuclide therapy (PRRT) could result in altered [177Lu]Lu-HA-DOTATATE uptake in tumors and organs. Therefore, receptor expression status and effects of different (unlabeled) administered peptide amounts during PRRT need to be evaluated. The aim of this study was to assess potential receptor saturation during PRRT by comparing organ and tumor uptake after administration of [177Lu]Lu-HA-DOTATATE with low, standard and high administered peptide amounts in patients with advanced metastatic neuroendocrine tumors (NETs). METHODS: Data of NET patients that received 7.4 GBq 177-Lutetium labeled to a low or high amount of HA-DOTATATE were retrospectively included. From included patients other PRRT cycles, containing standard administered peptide amounts, were included for intra-patient comparison. Uptake quantification was performed for spleen, liver, kidney, bone marrow, blood pool and tumor lesions on post-treatment SPECT/CT scans. A paired Wilcoxon signed-rank test was performed to determine uptake differences between two adjacent cycles for each patient. RESULTS: Thirteen patients received [177Lu]Lu-HA-DOTATATE with a high administered peptide amount (mean 346 µg vs 178 µg standard peptide amount). Low peptide amounts were administered to fifteen patients (mean 109 µg vs 202 µg standard peptide amount). High administered peptide amount resulted in significantly lower [177Lu]Lu-HA-DOTATATE uptake in the spleen (p = 0.00012), kidney (p = 0.013) and tumor lesions (p < 0.0001) versus standard peptide amounts. For low administered peptide amount, uptake was increased in the spleen (p = 0.015), while tumor uptake was significantly reduced (p = 0.015) compared to uptake after administration of standard peptide amounts. CONCLUSIONS: These findings confirmed a peptide amount-dependent organ and tumor accumulation for [177Lu]Lu-HA-DOTATATE, with receptor saturation in spleen for high and standard peptide amounts, while tumor and kidney receptor saturation occur only with high administered peptide amounts. A high peptide amount (~ 350 µg) is not recommended for standard-dose PRRT and standard amounts (~ 200 µg) seem more suitable to achieve optimal tumor accumulation with limited organ uptake.