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The aim of the study was to increase the uptake of the SSTR2-targeted radioligand Lu-177-DOTATATE using the DNA methyltransferase inhibitor (DNMTi) 5-aza-2′-deoxycytidine (5-aza-dC) and the histone deacetylase inhibitor (HDACi) valproic acid (VPA). The HEKsst2 and PC3 cells were incubated with variable concentrations of 5-aza-dC and VPA to investigate the uptake of Lu-177-DOTATATE. Cell survival, subsequent to external X-rays (0.6 or 1.2 Gy) and a 24 h incubation with 57.5 or 136 kBq/mL Lu-177-DOTATATE, was investigated via colony formation assay to examine the effect of the epidrugs. In the case of stimulated HEKsst2 cells, the uptake of Lu-177-DOTATATE increased by a factor of 28 in comparison to the unstimulated cells. Further, stimulated HEKsst2 cells demonstrated lower survival fractions (factor 4). The survival fractions of the PC3 cells remained almost unchanged. VPA and 5-aza-dC did not induce changes to the intrinsic radiosensitivity of the cells after X-ray irradiation. Clear stimulatory effects on HEKsst2 cells were demonstrated by increased cell uptake of the radioligand and enhanced SST2 receptor quantity. In conclusion, the investigated approach is suitable to stimulate the somatostatin receptor expression and thus the uptake of Lu-177-DOTATATE, enabling a more efficient treatment for patients with poor response to peptide radionuclide therapy (PRRT).

Objective Long axial field-of-view (LAFOV) PET/CT showed improved performance resulting from higher sensitivity. The aim was to quantify the impact of using the full acceptance angle (UHS) in image reconstructions with the Biograph Vision Quadra LAFOV PET/CT (Siemens Healthineers) compared to the limited acceptance angle (high sensitivity mode, HS). Methods 38 oncological patients examined on a LAFOV Biograph Vision Quadra PET/CT were analysed. 15 patients underwent [18F]FDG-PET/CT, 15 patients underwent [18F]PSMA-1007 PET/CT, and 8 patients underwent [68Ga]Ga-DOTA-TOC PET/CT. Signal-to-noise ratio (SNR) and standardised uptake values (SUVmean/max/peak) were used to compare UHS and HS with different acquisition times. Results The SNR was significantly higher for UHS compared to HS over all acquisition times (SNR UHS/HS [18F]FDG: 1.35 ± 0.02, p < 0.001; [18F]PSMA-1007: 1.25 ± 0.02, p < 0.001; [68Ga]Ga-DOTA-TOC: 1.29 ± 0.02, p < 0.001). Conclusion UHS showed significantly higher SNR opening the possibility of halving short acquisition times. This is of advantage in further reduction of whole-body PET/CT acquisition.