WMIC 2015: First-in-human Study 2

First Clinical Trial on Safety and Feasibility of KDR-targeted Ultrasound Molecular Imaging in Patients with Breast and Ovarian Lesions
Presented by Juergen Willmann, M.D., Stanford University

Purpose: To assess if ultrasound molecular imaging (USMI) using a clinical grade human kinase domain receptor (KDR)-targeted microbubble (BR55, Bracco) is safe and allows assessment of KDR expression in patients with breast and ovarian lesions, using immunohistochemistry (IHC) as gold standard.
Methods: 21 women (34-66 yrs) with focal breast lesions and 24 women (48-79 yrs) with focal ovarian lesions were injected IV with BR55 (0.03-0.08 mL/kg bw) and 2D USMI of the target lesions was performed dynamically every 2 min starting 5 min after injection up to 29 min, using a linear 15L8 probe (Siemens) or endocavitary 1123 probe (Esaote). Normal breast tissues surrounding the lesion or the contralateral normal ovary served as intra-patient controls. Blood pressure, EKG, oxygen levels, heart rate, CBC, and metabolic panel were obtained before, and 30 min, 1h, 24h after BR55 administration. Persistent focal BR55 binding on USMI was visually assessed in consensus by 2 blinded radiologists as none, possibly or definitely. Patients underwent surgical resection and tissues were stained for CD31 and KDR. A pathologist assessed vascular KDR expression using a 4-point scale (none, weak, intermediate, high).
Results: USMI with BR55 was well tolerated by all patients at all doses, without safety concerns. Among the 40 patients included in the analysis, KDR expression was higher in malignant breast and ovarian lesions (score 2.40±0.63 and 2.08±0.64, respectively) compared to benign breast and ovarian lesions (2.08±0.64 and 1.33±0.50). KDR expression matched well with presence of focal BR55 binding on USMI in malignant breast (13/15; 86.7%) and ovarian (11/13; 84.6%) lesions, as well as benign breast (2/3; 66.7%) and ovarian (8/9; 88.9%) lesions. Focal USMI signal could be detected up to 29 min after injection.
Conclusion: Use of BR55 in USMI of breast and ovarian lesions is safe and feasible and preliminary data indicate that KDR-targeted USMI signal matches well with vascular KDR expression on IHC.

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