Transitioning from CA to NCA 177Lu in the preparation of [177Lu]Lu-DOTATATE for PRRT - observations and considerations from a retrospective review.

Abstract

Peptide receptor radionuclide therapy (PRRT) with [¹⁷⁷Lu]Lu-DOTATATE is a well-established treatment for advanced gastroenteropancreatic neuroendocrine tumours. After transition from a carrier added (CA) ¹⁷⁷Lu formulation to a no-carrier added (NCA) ¹⁷⁷Lu formulation, increases in spleen and kidney standardised uptake values (SUV) were observed. This study aimed to evaluate these changes. This retrospective single-centre study reviewed 166 patients that received PRRT at St George Hospital from 03/2021 to 09/2024 using either CA (74 patients) or NCA (92 patients) [¹⁷⁷Lu]Lu-DOTATATE. Individual dose peptide content was compared to SUVs for non-target organs (kidneys and spleen) calculated from post-therapy quantitative SPECT/CT imaging. Patients were also assessed for 'cold' somatostatin analogue (SSA) received as standard treatment. A significant spleen SUV increase (p<0.001) was observed between patients receiving CA (high peptide concentration) and NCA (low peptide concentration) formulations. A moderate correlation was identified between decreasing administered DOTATATE and increasing splenic SUV (r=- 0.60). A lesser, but significant, difference was noted in the kidneys between CA and NCA preparations (p<0.001). Patients receiving NCA formulations with recent SSA demonstrated a significant increase in spleen SUV between initial therapy cycles (p=0.002) compared to those receiving no SSA. Those receiving CA with recent SSA saw a non-significant increase (p=0.37). Renal SUVs also saw a non-significant increase for CA (p=0.58) and NCA (p=0.50) preparations regardless of SSA treatment. Observed differences in SUV are likely due to variations in administered peptide mass (due to formulation differences and SSA treatment) leading to competition for receptors between radiolabelled [¹⁷⁷Lu]Lu-DOTATATE and 'cold' peptide. The optimisation of peptide mass has the potential to minimise radiation dose to healthy tissue and organs.