Direct Intra-Patient Comparison of Scaffold Protein-Based Tracers, [ 99m Tc]Tc-ADAPT6 and [ 99m Tc]Tc-(HE) 3 -G3, for Imaging of HER2-Positive Breast Cancer.

Previous Phase I clinical evaluations of the radiolabelled scaffold proteins [ 99m Tc]Tc-ADAPT6 and DARPin [ 99m Tc]Tc-(HE) 3 -G3 in breast cancer patients have demonstrated their safety and indicated their capability to discriminate between HER2-positive and HER2-negative tumours. The objective of this study was to compare the imaging of HER2-positive tumours in the same patients using [ 99m Tc]Tc-ADAPT6 and [ 99m Tc]Tc-(HE) 3 -G3. Eleven treatment-naïve female patients (26-65 years) with HER2-positive primary and metastatic breast cancer were included in the study. Each patient was intravenously injected with [ 99m Tc]Tc-ADAPT6, followed by an [ 99m Tc]Tc-(HE) 3 -G3 injection 3-4 days later and chest SPECT/CT was performed. All primary tumours were clearly visualized using both tracers. The uptake of [ 99m Tc]Tc-ADAPT6 in primary tumours (SUVmax = 4.7 ± 2.1) was significantly higher ( p < 0.005) than the uptake of [ 99m Tc]Tc-(HE) 3 -G3 (SUVmax = 3.5 ± 1.7). There was no significant difference in primary tumour-to-contralateral site values for [ 99m Tc]Tc-ADAPT6 (15.2 ± 7.4) and [ 99m Tc]Tc-(HE) 3 -G3 (19.6 ± 12.4). All known lymph node metastases were visualized using both tracers. The uptake of [ 99m Tc]Tc-ADAPT6 in all extrahepatic soft tissue lesions was significantly ( p < 0.0004) higher than the uptake of [ 99m Tc]Tc-(HE) 3 -G3. In conclusion, [ 99m Tc]Tc-ADAPT6 and [ 99m Tc]Tc-(HE) 3 -G3 are suitable for the visualization of HER2-positive breast cancer. At the selected time points, [ 99m Tc]Tc-ADAPT6 has a significantly higher uptake in soft tissue lesions, which might be an advantage for the visualization of small metastases.