Dataset Information

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.

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.

SUBMITTER: Bragina O

PROVIDER: S-EPMC10296685 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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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.

Bragina Olga O Chernov Vladimir V Schulga Alexey A Konovalova Elena E Hober Sophia S Deyev Sergey S Sörensen Jens J Tolmachev Vladimir V

Cancers 20230611 12

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 tr ...[more]

PMID: 37370758

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Project description:Most epithelial tumors recruit fibroblasts and other nonmalignant cells and activate them into cancer-associated fibroblasts. This often leads to overexpression of the membrane serine protease fibroblast-activating protein (FAP). It has already been shown that DOTA-bearing FAP inhibitors (FAPIs) generate high-contrast images with PET/CT scans. Since SPECT is a lower-cost and more widely available alternative to PET, 99mTc-labeled FAPIs represent attractive tracers for imaging applications in a larger number of patients. Furthermore, the chemically homologous nuclide 188Re is available from generators, which allows FAP-targeted endoradiotherapy. Methods: For the preparation of 99mTc-tricarbonyl complexes, a chelator was selected whose carboxylic acids can easily be converted into various derivatives in the finished product, enabling a platform strategy based on the original tracer. The obtained 99mTc complexes were investigated in vitro by binding and competition experiments on FAP-transfected HT-1080 (HT-1080-FAP) or on mouse FAP-expressing (HEK-muFAP) and CD26-expressing (HEKCD26) HEK cells and characterized by planar scintigraphy and organ distribution studies in tumor-bearing mice. Furthermore, a first-in-humans application was done on 2 patients with ovarian and pancreatic cancer, respectively. Results: 99mTc-FAPI-19 showed specific binding to recombinant FAP-expressing cells with high affinity. Unfortunately, liver accumulation, biliary excretion, and no tumor uptake were observed on planar scintigraphy for a HT-1080-FAP-xenotransplanted mouse. To improve the pharmacokinetic properties, hydrophilic amino acids were attached to the chelator moiety of the compound. The resulting 99mTc-labeled FAPI tracers revealed excellent binding properties (≤45% binding; >95% internalization), high affinity (half-maximal inhibitory concentration, 6.4-12.7 nM), and significant tumor uptake (≤5.4% injected dose per gram of tissue) in biodistribution studies. The lead candidate 99mTc-FAPI-34 was applied for diagnostic scintigraphy and SPECT of patients with metastasized ovarian and pancreatic cancer for follow-up to therapy with 90Y-FAPI-46. 99mTc-FAPI-34 accumulated in the tumor lesions, as also shown on PET/CT imaging using 68Ga-FAPI-46. Conclusion: 99mTc-FAPI-34 represents a powerful tracer for diagnostic scintigraphy, especially when PET imaging is not available. Additionally, the chelator used in this compound allows labeling with the therapeutic nuclide 188Re, which is planned for the near future.

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Dataset Information

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.

Publications

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

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