Ultrasound Molecular Imaging With BR55 in Patients With Breast and Ovarian Lesions: First-in-Human Results

Antonia Carla Testa, Guido Rindi, Maurizio Martini, Lorenzo Bonomo, Gianluigi Petrone, Jürgen K. Willmann, Keerthi S. Valluru, Amelie M. Lutz, Sanjiv S. Gambhir

Risultato della ricerca: Contributo in rivistaArticolo in rivista

109 Citazioni (Scopus)


Purpose We performed a first-in-human clinical trial on ultrasound molecular imaging (USMI) in patients with breast and ovarian lesions using a clinical-grade contrast agent (kinase insert domain receptor [KDR] -Targeted contrast microbubble [MBKDR]) that is targeted at the KDR, one of the key regulators of neoangiogenesis in cancer. The aim of this study was to assess whether USMI using MBKDR is safe and allows assessment of KDR expression using immunohistochemistry (IHC) as the gold standard. Methods Twenty-four women (age 48 to 79 years) with focal ovarian lesions and 21 women (age 34 to 66 years) with focal breast lesions were injected intravenously with MB KDR (0.03 to 0.08 mL/kg of body weight), and USMI of the lesions was performed starting 5 minutes after injection up to 29 minutes. Blood pressure, ECG, oxygen levels, heart rate, CBC, and metabolic panel were obtained before and after MBKDR administration. Persistent focal MBKDR binding on USMI was assessed. Patients underwent surgical resection of the target lesions, and tissues were stained for CD31 and KDR by IHC. Results USMI withMBKDR was well tolerated by all patients without safety concerns. Among the 40 patients included in the analysis, KDR expression on IHC matched well with imaging signal on USMI in 93% of breast and 85% of ovarian malignant lesions. Strong KDR-Targeted USMI signal was present in 77% of malignant ovarian lesions, with no targeted signal seen in 78% of benign ovarian lesions. Similarly, strong targeted signal was seen in 93% of malignant breast lesions with no targeted signal present in 67% of benign breast lesions. Conclusion USMI with MBKDR is clinically feasible and safe, and KDR-Targeted USMI signal matches well with KDR expression on IHC. This study lays the foundation for a new field of clinical USMI in cancer.
Lingua originaleEnglish
pagine (da-a)2133-2140
Numero di pagine8
RivistaJournal of Clinical Oncology
Stato di pubblicazionePubblicato - 2017


  • Breast Neoplasms / diagnostic imaging*


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