Phase I Study of 99mTc-ADAPT6, a Scaffold Protein-Based Probe for Visualization of HER2 Expression in Breast Cancer

Olga Bragina, Emma von Witting, Javad Garousi, Roman Zelchan, Mattias Sandström, Anna Orlova, Anna Medvedeva, Artem Doroshenko, Anzhelika Vorobyeva, Sarah Lindbo, Jesper Borin, Natalya Tarabanovskaya, Jens Sörensen, Sophia Hober, Vladimir Chernov, Vladimir Tolmachev

Результат исследований: Материалы для журналаСтатьярецензирование

3 Цитирования (Scopus)


Radionuclide molecular imaging of human epidermal growth factor receptor type 2 (HER2) expression may help to stratify breast and gastroesophageal cancer patients for HER2-targeting therapies. Albumin-binding domain-derived affinity proteins (ADAPTs) are a new type of small (46-59 amino acids) protein useful as probes for molecular imaging. The aim of this first-in-humans study was to evaluate the biodistribution, dosimetry, and safety of the HER2-specific 99mTc-ADAPT6. Methods: Twenty-nine patients with primary breast cancer were included. In 22 patients with HER2-positive (n = 11) or HER2-negative (n = 11) histopathology, an intravenous injection of 385 ± 125 MBq of 99mTc-ADAPT6 was performed, randomized to an injected protein mass of either 500 μg (n = 11) or 1,000 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 were well tolerated at all mass levels and not associated with adverse effects. 99mTc-ADAPT6 cleared rapidly from the blood and most other tissues. The normal organs with the highest accumulation were the 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 1,000 μg, respectively. Injection of 500 μg resulted in excellent discrimination between HER2-positive and HER2-negative tumors as early as 2 h after injection (tumor-to-contralateral breast ratio, 37 ± 19 vs. 5 ± 2; P < 0.01). The tumor-to-contralateral breast ratios for HER2-positive tumors were significantly (P < 0.05) higher for an injected mass of 500 μg than for either 250 or 1,000 μg. 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. Further studies are justified to evaluate whether 99mTc-ADAPT6 can be used as an imaging probe to stratify patients for HER2-targeting therapy in areas where PET imaging is not readily available.

Язык оригиналаАнглийский
Страницы (с-по)493-499
Число страниц7
ЖурналJournal of nuclear medicine : official publication, Society of Nuclear Medicine
Номер выпуска4
СостояниеОпубликовано - 1 апр 2021

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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