title: Ultrasound Molecular Imaging With BR55 in Patients With Breast and Ovarian Lesions: First-in-Human Results.
abstract: 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 MBKDRis 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 MBKDR(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 MBKDRadministration. Persistent focal MBKDRbinding on USMI was assessed. Patients underwent surgical resection of the target lesions, and tissues were stained for CD31 and KDR by IHC. Results USMI with MBKDRwas 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 MBKDRis 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.
authors.affiliation: Jürgen K. Willmann, Keerthi S. Valluru, Amelie M. Lutz, and Sanjiv S. Gambhir, Stanford University, Stanford, CA; and Lorenzo Bonomo, Antonia Carla Testa, Pierluigi Rinaldi, Guido Rindi, Gianluigi Petrone, and Maurizio Martini, Universitary Policlinic A. Gemelli-Foundation, Catholic University, Rome, Italy.
authors.forename: Jürgen K
authors.initials: JK
authors.lastname: Willmann
authors.affiliation: Jürgen K. Willmann, Keerthi S. Valluru, Amelie M. Lutz, and Sanjiv S. Gambhir, Stanford University, Stanford, CA; and Lorenzo Bonomo, Antonia Carla Testa, Pierluigi Rinaldi, Guido Rindi, Gianluigi Petrone, and Maurizio Martini, Universitary Policlinic A. Gemelli-Foundation, Catholic University, Rome, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Bonomo
authors.affiliation: Jürgen K. Willmann, Keerthi S. Valluru, Amelie M. Lutz, and Sanjiv S. Gambhir, Stanford University, Stanford, CA; and Lorenzo Bonomo, Antonia Carla Testa, Pierluigi Rinaldi, Guido Rindi, Gianluigi Petrone, and Maurizio Martini, Universitary Policlinic A. Gemelli-Foundation, Catholic University, Rome, Italy.
authors.forename: Antonia Carla
authors.initials: AC
authors.lastname: Testa
authors.affiliation: Jürgen K. Willmann, Keerthi S. Valluru, Amelie M. Lutz, and Sanjiv S. Gambhir, Stanford University, Stanford, CA; and Lorenzo Bonomo, Antonia Carla Testa, Pierluigi Rinaldi, Guido Rindi, Gianluigi Petrone, and Maurizio Martini, Universitary Policlinic A. Gemelli-Foundation, Catholic University, Rome, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Rinaldi
authors.affiliation: Jürgen K. Willmann, Keerthi S. Valluru, Amelie M. Lutz, and Sanjiv S. Gambhir, Stanford University, Stanford, CA; and Lorenzo Bonomo, Antonia Carla Testa, Pierluigi Rinaldi, Guido Rindi, Gianluigi Petrone, and Maurizio Martini, Universitary Policlinic A. Gemelli-Foundation, Catholic University, Rome, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Rindi
authors.affiliation: Jürgen K. Willmann, Keerthi S. Valluru, Amelie M. Lutz, and Sanjiv S. Gambhir, Stanford University, Stanford, CA; and Lorenzo Bonomo, Antonia Carla Testa, Pierluigi Rinaldi, Guido Rindi, Gianluigi Petrone, and Maurizio Martini, Universitary Policlinic A. Gemelli-Foundation, Catholic University, Rome, Italy.
authors.forename: Keerthi S
authors.initials: KS
authors.lastname: Valluru
authors.affiliation: Jürgen K. Willmann, Keerthi S. Valluru, Amelie M. Lutz, and Sanjiv S. Gambhir, Stanford University, Stanford, CA; and Lorenzo Bonomo, Antonia Carla Testa, Pierluigi Rinaldi, Guido Rindi, Gianluigi Petrone, and Maurizio Martini, Universitary Policlinic A. Gemelli-Foundation, Catholic University, Rome, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Petrone
authors.affiliation: Jürgen K. Willmann, Keerthi S. Valluru, Amelie M. Lutz, and Sanjiv S. Gambhir, Stanford University, Stanford, CA; and Lorenzo Bonomo, Antonia Carla Testa, Pierluigi Rinaldi, Guido Rindi, Gianluigi Petrone, and Maurizio Martini, Universitary Policlinic A. Gemelli-Foundation, Catholic University, Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Martini
authors.affiliation: Jürgen K. Willmann, Keerthi S. Valluru, Amelie M. Lutz, and Sanjiv S. Gambhir, Stanford University, Stanford, CA; and Lorenzo Bonomo, Antonia Carla Testa, Pierluigi Rinaldi, Guido Rindi, Gianluigi Petrone, and Maurizio Martini, Universitary Policlinic A. Gemelli-Foundation, Catholic University, Rome, Italy.
authors.forename: Amelie M
authors.initials: AM
authors.lastname: Lutz
authors.affiliation: Jürgen K. Willmann, Keerthi S. Valluru, Amelie M. Lutz, and Sanjiv S. Gambhir, Stanford University, Stanford, CA; and Lorenzo Bonomo, Antonia Carla Testa, Pierluigi Rinaldi, Guido Rindi, Gianluigi Petrone, and Maurizio Martini, Universitary Policlinic A. Gemelli-Foundation, Catholic University, Rome, Italy.
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000201:enzymology; D003287:Contrast Media; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods*; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging* / Q000201:enzymology; D011446:Prospective Studies; D014463:Ultrasonography / Q000379:methods*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis
chemical_list: D003287:Contrast Media; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2