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

Olga Bragina; Vladimir Chernov; Alexey Schulga; Elena Konovalova; Sophia Hober; Sergey Deyev; Jens Sörensen; Vladimir Tolmachev

doi:10.3390/cancers15123149

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

Cancers (Basel). 2023 Jun 11;15(12):3149. doi: 10.3390/cancers15123149.

Authors

Olga Bragina^{1

2}, Vladimir Chernov^{1

2}, Alexey Schulga^{2

3}, Elena Konovalova^{2

3}, Sophia Hober⁴, Sergey Deyev^{2

3}, Jens Sörensen⁵, Vladimir Tolmachev^{2

6}

Affiliations

¹ Department of Nuclear Therapy and Diagnostic, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 Tomsk, Russia.
² Research Centrum for Oncotheranostics, Research School of Chemistry and Applied Biomedical Sciences, Tomsk Polytechnic University, 634050 Tomsk, Russia.
³ Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.
⁴ Department of Protein Science, KTH Royal Institute of Technology, 100 44 Stockholm, Sweden.
⁵ Department of Surgical Sciences, Nuclear Medicine & PET, Uppsala University, 751 85 Uppsala, Sweden.
⁶ Department of Immunology, Genetics and Pathology, Uppsala University, 752 37 Uppsala, Sweden.

Abstract

Previous Phase I clinical evaluations of the radiolabelled scaffold proteins [^99mTc]Tc-ADAPT6 and DARPin [^99mTc]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 [^99mTc]Tc-ADAPT6 and [^99mTc]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 [^99mTc]Tc-ADAPT6, followed by an [^99mTc]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 [^99mTc]Tc-ADAPT6 in primary tumours (SUVmax = 4.7 ± 2.1) was significantly higher (p < 0.005) than the uptake of [^99mTc]Tc-(HE)₃-G3 (SUVmax = 3.5 ± 1.7). There was no significant difference in primary tumour-to-contralateral site values for [^99mTc]Tc-ADAPT6 (15.2 ± 7.4) and [^99mTc]Tc-(HE)₃-G3 (19.6 ± 12.4). All known lymph node metastases were visualized using both tracers. The uptake of [^99mTc]Tc-ADAPT6 in all extrahepatic soft tissue lesions was significantly (p < 0.0004) higher than the uptake of [^99mTc]Tc-(HE)₃-G3. In conclusion, [^99mTc]Tc-ADAPT6 and [^99mTc]Tc-(HE)₃-G3 are suitable for the visualization of HER2-positive breast cancer. At the selected time points, [^99mTc]Tc-ADAPT6 has a significantly higher uptake in soft tissue lesions, which might be an advantage for the visualization of small metastases.

Keywords: ADAPT6; DARPin; HER2; clinical study; radionuclide molecular imaging; scaffold proteins; technetium-99m.

Abstract

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