Relationships between uptake of [⁶⁸Ga]Ga-DOTA-TATE and absorbed dose in [¹⁷⁷Lu]Lu-DOTA-TATE therapy

Background: Somatostatin receptor Ga-68 PET imaging is standard for evaluation of a patient's suitability for Lu-177 peptide receptor radionuclide therapy of neuroendocrine tumours (NETs). The Ga-68 PET serves to ensure sufficient somatostatin receptor expression, commonly evaluated qualitatively. The aim of this study is to investigate the quantitative relationships between uptake in Ga-68 PET and absorbed doses in Lu-177 therapy. Method: Eighteen patients underwent [Ga-68]Ga-DOTA-TATE PET imaging within 20 weeks prior to their first cycle of [Lu-177]Lu-DOTA-TATE. Absorbed doses for therapy were estimated for tumours, kidney, spleen, and normal liver parenchyma using a hybrid SPECT/CT-planar method. Gallium-68 activity concentrations were retrieved from PET images and also used to calculate SUVs and normalized SUVs, using blood and tissue for normalization. The Ga-68 activity concentrations per injected activity, SUVs, and normalized SUVs were compared with Lu-177 activity concentrations 1 d post-injection and Lu-177 absorbed doses. For tumours, for which there was a variable number per patient, both inter- and intra-patient correlations were analysed. Furthermore, the prediction of Lu-177 tumour absorbed doses based on a combination of tumour-specific Ga-68 activity concentrations and group-based estimates of the effective half-lives for grade 1 and 2 NETs was explored. Results: For normal organs, only spleen showed a significant correlation between the Ga-68 activity concentration and Lu-177 absorbed dose (r = 0.6). For tumours, significant, but moderate, correlations were obtained, with respect to both inter-patient (r = 0.7) and intra-patient (r = 0.45) analyses. The correlations to absorbed doses did not improve when using Ga-68 SUVs or normalized SUVs. The relationship between activity uptakes for Ga-68 PET and Lu-177 SPECT was stronger, with correlation coefficients r = 0.8 for both inter- and intra-patient analyses. The Lu-177 absorbed dose to tumour could be predicted from the Ga-68 activity concentrations with a 95% coverage interval of - 65% to 248%. Conclusions: On a group level, a high uptake of [Ga-68]Ga-DOTA-TATE is associated with high absorbed doses at Lu-177-DOTA-TATE therapy, but the relationship has a limited potential with respect to individual absorbed dose planning. Using SUV or SUV normalized to reference tissues do not improve correlations compared with using activity concentration per injected activity.