Comparative analysis of the use of technetium-99m labeled recombinant target molecules at doses of 1000 and 2000 μg for radionuclide diagnostics of HER2-positive breast cancer

Materials and methods. The study included 18 patients with breast cancer (T1–4N0–2M0) before systemic treatment: 10 — with HER2/neu overexpression; 8 — HER2/neu negative. In all cases, morphological, immunohistochemical studies, as well as FISH analysis of the primary tumor were performed. All patients underwent radionuclide studies (planar scintigraphy and SPECT of the chest) at 2, 4, 6 and 24 hours after injection of the «99mTc-DARPinG3» in dosages of 1000 and 2000 μg.Results. The half-life of the labeled protein from the blood was 3.5 hours for a dosage of 1000 μg; 3.8 h — for 2000 mcg. The organ with the highest absorption of «99mTc-DARPinG3» was the kidneys, regardless of the protein dose (0.10±0.02 and 0.10±0.03 mGy, respectively). The effective dose for 1000 μg was 0.011±0.001 mGy; for 2000 μg — 0.012±0.006. The liver absorption dose was significantly higher with 1000 μg of protein compared to 2000 μg (p<0.005, Mann–Whitney U test). The tumor/background ratio was significantly higher at 2 and 4 hours after administration of the «99mTc-DARPinG3» in patients with HER2-positive tumors in 1000 and 2000 μg doses of protein (p<0.005, Mann–Whitney U test).Conclusion. Clinical studies of the «99mTc-DARPinG3» in dosages of 1000 and 2000 μg demonstrated rapid elimination from the bloodstream and effective doses comparable to those obtained in the study with others alternative scaffold proteins labeled with various isotopes. An essential point of this work is the positive correlation of the protein dose with the accumulation of the compound in the liver, which is important component in diagnostic and allows to detect tumor sites in liver.