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Phase I study of 99...
Phase I study of 99mTc-ADAPT6, a scaffold protein-based probe for visualization of HER2 expression in breast cancer
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Bragina, Olga (author)
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- von Witting, Emma (author)
- KTH,Proteinvetenskap
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Garousi, Javad (author)
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Zelchan, Roman (author)
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Sandström, Mattias (author)
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Orlova, Anna (author)
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Medvedeva, Anna (author)
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Doroshenko, Artem (author)
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Vorobyeva, Anzhelika (author)
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Lindbo, Sarah (author)
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Borin, Jesper (author)
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Tarabanovskaya, Natalya (author)
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- Hober, Sophia, 1965- (author)
- KTH,Proteinteknologi
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Chernov, Vladimir (author)
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Tolmachev, Vladimir (author)
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(creator_code:org_t)
- English.
- Related links:
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https://urn.kb.se/re...
Abstract
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- 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 HER2-specific 99mTc-ADAPT6.METHODS. Twenty-two patients with HER2-positive (n=11) or HER2-negative (n=11) primary breast cancer were intravenously injected with 385125 MBq. The injected amount of protein was 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 received a dose of 250 μg, and the planar scintigraphy followed by SPECT imaging was performed after 2 h only.RESULTS. Injection of 99mTc-ADAPT6 was well tolerated for all doses evaluated in the study, and was not associated with any adverse effects. 99mTc-ADAPT6 cleared rapidly from the blood and the majority of tissues. The normal organs with the highest accumulation were kidney, liver and lung. The effective doses were determined to 0.0090.002 and 0.0100.003 mSv/MBq when injecting protein amounts 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 3719 vs 52, p < 0.01). The tumor-to-contralateral breast ratios for HER2-positive tumors were significantly (p < 0.5) higher for the injected mass of 500 μg than for both 250 and 1000 μg. In one patient, the imaging using 99mTc-ADAPT6 revealed three bone metastases, which were not found at the time of diagnosis by CT or 99mTcpyrophosphate bone scan. MRI imaging confirmed this finding.CONCLUSION. Injections of 99mTc-ADAPT6 are safe and associated with low absorbed and effective doses. A protein dose of 500 μg is preferable for discrimination between tumors with high and low expression of HER2. 99mTc-ADAPT6 is a promising imaging probe for the stratification of patients for HER2-targeting therapy.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- HER2
- ADAPT6
- 99mTc
- SPECT
- Phase I
- Bioteknologi
- Biotechnology
Publication and Content Type
- vet (subject category)
- ovr (subject category)
To the university's database
- By the author/editor
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Bragina, Olga
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von Witting, Emm ...
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Garousi, Javad
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Zelchan, Roman
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Sandström, Matti ...
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Orlova, Anna
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show more...
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Medvedeva, Anna
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Doroshenko, Arte ...
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Vorobyeva, Anzhe ...
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Lindbo, Sarah
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Borin, Jesper
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Tarabanovskaya, ...
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Hober, Sophia, 1 ...
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Chernov, Vladimi ...
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Tolmachev, Vladi ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- By the university
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Royal Institute of Technology