TY - JOUR T1 - Phase I trial of <sup>99m</sup>Tc-(HE)<sub>3</sub>-G3, a DARPin-based probe for imaging of HER2 expression in breast cancer JF - Journal of Nuclear Medicine JO - J Nucl Med DO - 10.2967/jnumed.121.262542 SP - jnumed.121.262542 AU - Olga Bragina AU - Vladimir Chernov AU - Alexey Schulga AU - Elena Konovalova AU - Eugeniy Garbukov AU - Anzhelika Vorobyeva AU - Anna Orlova AU - Liubov Tashireva AU - Jens Sorensen AU - Roman Zelchan AU - Anna Medvedeva AU - Sergey Deyev AU - Vladimir Tolmachev Y1 - 2021/08/01 UR - http://jnm.snmjournals.org/content/early/2021/08/12/jnumed.121.262542.abstract N2 - Radionuclide molecular imaging of human epidermal growth factor type 2 (HER2) expression may enable a non-invasive discrimination between HER2-positive and HER2-negative breast cancers for stratification of patients for HER2-targeted treatments. DARPin G3 is a small (molecular weigh 14 kDa) scaffold protein with picomolar affinity to HER2. The aim of this first-in-human study was to evaluate the safety, biodistribution and dosimetry of 99mTc-(HE)3-G3. Methods: Three cohorts of patients with primary breast cancer (each including at least 4 patients with HER2-negative and 5 patients with HER2-positive tumors) were injected with either 1000, 2000 or 3000 µg of 99mTc-(HE)3-G3 (287±170 MBq). Whole-body planar imaging followed by SPECT was performed at 2, 4, 6 and 24 h after injection. Vital signs and possible side effects were monitored during imaging and up to 7 days after injection. Results: All injections were well tolerated. No side effects were observed. The results of blood and urine analyses did not differ before and after studies. 99mTc-(HE)3-G3 cleared rapidly from the blood. The highest uptake was detected in the kidneys and liver followed by the lungs, breasts and small intestinal content. The hepatic uptake after injecting with 2000 or 3000 µg was significantly (p&lt;0.05) lower than the uptake after injecting with 1000 µg. Effective doses did not differ significantly between cohorts (average 0.011± 0.004 mSv/MBq). Tumor-to-contralateral site ratios for HER-positive tumors were significantly (p&lt; 0.05) higher than for HER2-negative at 2 and 4 h after injection. Conclusion: Imaging of HER2 expression using 99mTc-(HE)3-G3 is safe, well-tolerated and provides a low absorbed dose burden on patients. This imaging enables discerning HER2-positive and HER2-negative breast cancer. Phase I study data justifies further clinical development of 99mTc-(HE)3-G3. ER -