Phase I Study of 99mTc-ADAPT6, a Scaffold Protein–Based Probe for Visualization of HER2 Expression in Breast Cancer
| Autor: | Anzhelika Vorobyeva, Javad Garousi, Sophia Hober, Mattias Sandström, A. V. Doroshenko, Sarah Lindbo, Vladimir M. Chernov, Jesper Borin, Olga Bragina, Roman Zelchan, Jens Nørkær Sørensen, Anna Orlova, A. V. Medvedeva, Emma von Witting, Vladimir Tolmachev, Natalya Tarabanovskaya |
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| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
Kidney Biodistribution Lung business.industry medicine.disease 030218 nuclear medicine & medical imaging 03 medical and health sciences 0302 clinical medicine Breast cancer medicine.anatomical_structure 030220 oncology & carcinogenesis Spect imaging medicine Radiology Nuclear Medicine and imaging Histopathology Molecular imaging skin and connective tissue diseases Nuclear medicine business Adverse effect |
| Zdroj: | Journal of Nuclear Medicine. 62:493-499 |
| ISSN: | 2159-662X 0161-5505 |
| Popis: | Radionuclide molecular imaging of human epidermal growth factor (HER2) expression may be helpful to stratify breast and gastroesophageal cancer patients for HER2-targeting therapies. ADAPTs (albumin-binding domain derived affinity proteins) are a new type of small (46-59 amino acids) proteins useful as probes for molecular imaging. The aim of this first-in-human study was to evaluate biodistribution, dosimetry, and safety of the HER2-specific 99mTc-ADAPT6. METHODS: Twenty-nine patients with primary breast cancerwere included. In 22 patients with HER2-positive (n = 11) or HER2-negative (n = 11) histopathology an intravenous injection with 385±125 MBq 99mTc-ADAPT6 was performed, randomized to an injected protein mass of either 500 µg (n = 11) or 1000 µg (n = 11). Planar scintigraphy followed by SPECT imaging was performed after 2, 4, 6 and 24 h. An additional cohort (n = 7) was injected with 165±29 MBq (injected protein mass 250 µg) and imaging was performed after 2 h only. RESULTS: Injections of 99mTc-ADAPT6 at all injected mass levels were well tolerated and not associated with adverse effects. 99mTc-ADAPT6 cleared rapidly from blood and most other tissues. The normal organs with the highest accumulation were kidney, liver and lung. Effective doses were 0.009±0.002 and 0.010±0.003 mSv/MBq for injected protein masses of 500 and 1000 µg, respectively. Injection of 500 µg resulted in excellent discrimination between HER2-positive and HER2-negative tumors already 2 h after injection (tumor-to-contralateral breast ratio was 37±19 vs 5±2, p |
| Databáze: | OpenAIRE |
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