Phase II clinical study of DD-723 (perflubutane): dose-response study in patients with breast tumors.
OBJECTIVE
We compared the contrast effect of three doses of DD-723 in subjects with breast tumors to determine the recommended dose. We then evaluated differential diagnosis results using plain ultrasonography, contrast-enhanced ultrasonography (plain + enhanced), and contrast-enhanced magnetic resonance imaging (MRI) compared to the pathological diagnosis.


METHODS
To evaluate the contrast effect, contrast-enhanced ultrasonic images were independently evaluated in a randomized sequence by three blinded reviewers trained in the evaluation method beforehand. Multiple evaluation results from the three reviewers were used to assess the overall contrast effect. The differential diagnosis was evaluated independently by three blinded reviewers using contrast-enhanced ultrasonic images and contrast-enhanced magnetic resonance images in a randomized sequence; reviewers were also blinded to subject characteristics. Multiple evaluation results from the three reviewers were used to assess the overall differential diagnosis.


RESULTS
The recommended dose of DD-723 is an intermediate dose of 0.12 μL MB/kg. Accuracy, sensitivity, and specificity were improved more in the differential diagnosis by contrast-enhanced ultrasonography than in plain ultrasonography. Accuracy and specificity were better and sensitivity similar compared to contrast-enhanced MRI.


CONCLUSIONS
An intermediate dose showed the highest efficacy in terms of overall contrast effect. Contrast-enhanced ultrasonography is safe and useful when used in differential diagnosis.
Department of Diagnostic Imaging, Jikei University Hospital, 3-19-18 Nishishinbashi, Minato, Tokyo, 105-8471, Japan. miyamoto@jikei.ac.jp.
Yukio
Y
Miyamoto
Department of Surgery, Rinku General Medical Center, Osaka, Japan.
Toshikazu
T
Ito
Center of Medical Ultrasonics, Dokkyo Medical University, Tochigi, Japan.
Etsuo
E
Takada
Department of Laboratory Medicine, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
Kiyoka
K
Omoto
Department of Endoscopy and Ultrasound, Nara Medical University Hospital, Nara, Japan.
Toshiko
T
Hirai
Department of Diagnostic Imaging, Tochigi Cancer Center, Tochigi, Japan.
Ryuzo
R
Sekiguchi
Kobe Urban Breast Clinic, Hyogo, Japan.
Toshitaka
T
Okuno
Department of Radiology, Toho University Omori Hospital, Tokyo, Japan.
Shinsaku
S
Kanazawa
Department of Diagnostic Imaging, Jikei University Hospital, 3-19-18 Nishishinbashi, Minato, Tokyo, 105-8471, Japan.
Norio
N
Nakata
Department of Diagnostic Imaging, Jikei University Hospital, 3-19-18 Nishishinbashi, Minato, Tokyo, 105-8471, Japan.
Takao
T
Igarashi
Breast tumors; Phase II clinical study; Sonazoid; Ultrasound contrast medium