PT - JOURNAL ARTICLE AU - Olga Bragina AU - Emma von Witting AU - Javad Garousi AU - Roman Zelchan AU - Mattias Sandström AU - Anna Orlova AU - Anna Medvedeva AU - Artem Doroshenko AU - Anzhelika Vorobyeva AU - Sarah Lindbo AU - Jesper Borin AU - Natalya Tarabanovskaya AU - Jens Sörensen AU - Sophia Hober AU - Vladimir Chernov AU - Vladimir Tolmachev TI - Phase I Study of <sup>99m</sup>Tc-ADAPT6, a Scaffold Protein–Based Probe for Visualization of HER2 Expression in Breast Cancer AID - 10.2967/jnumed.120.248799 DP - 2021 Apr 01 TA - Journal of Nuclear Medicine PG - 493--499 VI - 62 IP - 4 4099 - http://jnm.snmjournals.org/content/62/4/493.short 4100 - http://jnm.snmjournals.org/content/62/4/493.full SO - J Nucl Med2021 Apr 01; 62 AB - 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 &lt; 0.01). The tumor–to–contralateral breast ratios for HER2-positive tumors were significantly (P &lt; 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.