UNLABELLED: The present study was a proof-of-concept study to provide an initial indication of the efficacy and safety of imaging malignant breast tumors using (99m)Tc-NC100692. The agent is a small peptide with high affinity for integrin receptors that are upregulated and expressed preferentially on proliferating endothelial cells. METHODS: Sixteen patients with suggestive mammographic findings and 4 patients with benign lesions were included. The "standard of truth" was based on the histopathologic diagnosis of the recruited patients. All subjects received up to 75 microg of (99m)Tc-NC100692 with an average (99m)Tc activity of 694 MBq (range, 561-747 MBq). Safety endpoints were treatment-emergent adverse events (AEs) and changes in a limited physical examination, electrocardiogram (ECG) recordings, blood biochemistry, hematology, coagulation, vital signs, and urine analysis after administration of (99m)Tc-NC100692 and throughout the 24-h follow-up. Static images and SPECT were acquired between 40 min and 2.5 h after injection of the agent. Two experienced nuclear medicine physicians read the images in a nonblinded fashion. RESULTS: Nineteen of 22 malignant lesions were detected using (99m)Tc-NC100692 scintigraphy. Twenty lesions confirmed as malignant by histopathology were seen on mammography or ultrasound. Two additional lesions were identified from histopathology alone. Safety parameters evaluated through the follow-up period of 2.5 h included clinical laboratory tests, vital signs, and ECG. Five of 20 subjects experienced nonserious AEs, and all AEs were classified as mild. One subject experienced an AE (dysgeusia) possibly related to administration of (99m)Tc-NC100692. This AE was mild and lasted only for a few minutes. No deaths, serious AEs, or withdrawals due to AEs occurred during the study. CONCLUSION: Nineteen of 22 malignant lesions (86%) were clearly detected via scintigraphic imaging after administration of (99m)Tc-NC100692. Overall, the efficacy data in subjects with suspected breast lesions suggest that (99m)Tc-NC100692 scintigraphy may be effective in detecting malignant lesions. The use of (99m)Tc-NC100692 in subjects with breast cancer is safe and well tolerated. Further studies are warranted to assess the clinical potential of (99m)Tc-NC100692.