16 Two factors may confound the use of MBs for this application. The reported detection of malignant lesions with BR55 was 68%. BR55 was examined recently in a clinical study for its ability to detect PCa 16. One example of this approach currently in clinical trials is BR55 (Bracco, Geneva, Switzerland), 13– 15 which is targeted to vascular endothelial growth factor receptor-2 (VEGFR2). One option to improve these parameters is molecular targeting of microbubbles to vascular-biomarkers. 8– 10 Most of these efforts have utilized micron-sized UCAs or microbubbles (MBs), 9, 11, 12 which are already clinically utilized for other applications, but these have lacked specificity and sensitivity over conventional methods. 6, 7 In order to increase the PCa detection rate while limiting the number of biopsy procedures, significant effort has been focused on formulation of lipid and/or protein-stabilized gas-filled ultrasound contrast agents (UCAs) to improve the US imaging capability of cancer within the prostate. If the already-on board US technology can be used to more reliably identify the location of PCa within the prostate gland, these outcomes stand to be significantly improved.Ĭontrast-enhanced ultrasound has been investigated as one option for improved PCa detection. 3– 5 Concern over the lack of pathological data in the face of other positive clinical risk factors results in almost 50% of patients undergoing second, if not third and fourth, prostate biopsies leading to increased costs and risk associated with unnecessary procedures. These cores represent only 1% of prostate tissue and are a gross under sampling of prostate gland tissue, and biopsies performed using this conventional procedure result in significant false negatives of up to 50%. Accordingly, biopsies are performed in a systematic manner by selecting 6–12 or more area from the peripheral zone of the prostate. The standard PCa biopsy procedure uses transrectal ultrasound (US)-guidance to determine the prostate gland orientation, but the delineation of tumors within the prostate using US is unclear. Currently, men with an abnormal digital rectal exam and/or increased levels of prostate serum antigen (PSA) are considered at high risk for cancer and are referred for a prostate biopsy to assess if PCa is present. 1, 2 Accurate diagnosis of PCa is a crucial step necessary for informing the clinical management of the disease, yet conventional options leave much space for improvement.
Such demonstration of the immense yet underutilized potential of ultrasound in the molecular imaging area can open the door to future opportunities for improving sensitivity and specificity of cancer detection using parametric NB-enhanced ultrasound imaging.ĭespite significant efforts, prostate cancer (PCa) is still the second most common leading cause of cancer-related deaths worldwide, with 180,000 new cases diagnosed in the USA in 2018. Importantly, these processes could be visualized and quantified, in real-time, with clinical ultrasound. Results demonstrate that active targeting rapidly and selectively enhances tumor accumulation and tumor retention. The PSMA-targeted-NB (PSMA-NB) were utilized to simultaneously image dual-flank PCa (PSMA-positive PC3pip and PSMA-negative PC3flu) to examine whether the biomarker can be successfully detected and imaged in a mouse model. Here we report nanobubbles (NB) that specifically targets prostate specific membrane antigen (PSMA) overexpressed in PCa. Targeted nanoscale-contrast agents with improved capability to accumulate in tumors may result in prolonged signal enhancement and improved detection of PCa with ultrasound. Contrast-enhanced ultrasound with microbubbles has shown promise in detection of prostate cancer (PCa), but sensitivity and specificity remain challenging.
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