Comparative Analysis of the Clinical Use of 99mTechnetium-Labeled Recombinant Target Molecules in Different Dosages for the Radionuclide Diagnosis of Her2-Positive Breast Cancer

Abstract

Background. The chief goal in assessing the Her2/neu status in clinical practice is to identify indications for targeted therapy. The main methods for determining the Her2/neu status are an immunohistochemical method and fluorescence in situ hybridization (FISH); however, despite their widespread use, they have a number of significant disadvantages. Over the past few years, radionuclide diagnosis using a new class of alternative scaffold proteins that meet all the requirements for optimal radionuclide delivery to tumor cells has become widespread. Objective: comparative analysis of the effectiveness of radionuclide imaging of Her2-positive breast cancer using 99m technetium-labeled recombinant molecules in different dosages. Material and methods. The investigation enrolled 22 patients with breast cancer (T1-4N0-2M0) before systemic therapy: 11 had Her2/neu overexpression; 11 had no marker expression. The patients’ mean age was 50.7 ± 2.3 years. Morphological and immunohistochemical studies were performed in all cases. FISHanalysis was carried out in the presence of the Her2/neu 2+ value. The agent was prepared immediately before using in dosages of 500 and 1000 µg, after which it was slowly administered intravenously to the patient. Whole-body scintigraphy and chest single-photon emission computed tomography were conducted at 2, 4, 6 and 24 hours after administration. Results. The radiochemical yield and radiochemical purity values were 77 ± 9% and 99 ± 1%, respectively. The activity of the agent immediately before administration was 416 ± 135 MBq for the 500 µg group and 349 ± 133 MBq for 1000 µg group. Analysis of the findings indicated that the higher uptake of the agent by organs without tumor lesion was observed in the kidneys, liver, and lungs. The highest renal absorption of the agent was observed in both study groups (0.135 ± 0.042 and 0.191 ± 0.047 mGy, respectively). The effective dose was 0.009 ± 0.002 mGy for the 500 µg group and 0.010 ± 0.003 mGy for the 1000 µg group. The better distribution between the tumors with Her2/neu positive and negative statuses was observed 2 hours after administration in the 500 µg group with the mean tumor/background value of 37 ± 19 for Her2-positive tumors, and 5 ± 2 for Her2-negative tumors (p < 0.001). Conclusion. The findings suggest that the test radiopharmaceutical agent at a dose of 500 µg can be considered as a new additional method to diagnose Her2-positive breast tumors.