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By using an organic framework to fabricate functional biomaterials, novel design and advanced biomedical applications of polymeric microbubbles for in vivo targeting and disease-oriented imaging of tumor vascularization can be developed. The present study describes novel synthetic protocols to fabricate RGD (Arginine-Glycine-Aspartic)-tagged αvβ3-targeted ultrasound microbubbles. The microbubbles were synthesized by emulsion polymerization techniques. Two types of microbubbles (MBs-1 and MBs-2) were obtained via biotin-streptavidin conjugation to poly(butyl cyanoacrylate) microbubbles (MBs-0) obtained by one-step synthesis in reverse order. The size distributions and surface zeta potentials were characterized. The results showed that the sizes of the MBs-2 were larger than that those of the MBs-1, and the MBs-2 showed decreased charge compared to MBs-1. In cell targeting studies, MBs-2 exhibited relatively stronger targeting affinity for αvβ3 integrins, while MBs-1 showed weaker targeting capability. Furthermore, in vivo mice imaging using MBs-2 for intravenous injection exhibited an obvious and sustained signal increase, which revealed the accumulative of MBs-2 anchoring in tumor. Hence, MBs-2 have been proven to be a promising candidate for using as ultrasound contrast agents for the early diagnosis of αvβ3-overexpressing malignant tumors, including breast cancer.

Fetal hydronephrosis (HY) is a frequent congenital condition, which may be detected by prenatal ultrasound. Society for Fetal Urology (SFU) and anterior-posterior diameter (APD) grading are two major grading systems based on ultrasonography. The present study aimed to assess the predictive value of the SFU and APD grades in patients with fetal HY. A total of 162 patients with 234 kidneys affected by HY were included in the present study. The SFU and APD grades were determined from the ultrasound images at 38 gestational weeks, and a 12-month follow-up was performed after birth. The associations of the SFU and APD grades with the outcome of fetal HY, including HY regression, and post-partum surgery were examined. In the present study, 16 patients with 17 kidneys were diagnosed with pathological HY, and stenosis at the ureteropelvic junction was demonstrated to be a leading cause of pathological HY. Among the 234 kidneys affected by HY, 161 kidneys were scored as SFU grade I, 57 as SFU grade II, 7 as SFU grade III and 9 kidneys as SFU grade IV. According to the APD grading system, 112 kidneys were determined as having low, 104 as having moderate and 18 as having severe HY. The SFU and APD grades were demonstrated to be independently associated with the occurrence of pathological HY by logistic regression analysis with a high diagnostic accuracy to distinguish pathological and physiological HY cases as evidenced by the results of ROC analysis. In addition, univariate and multivariate logistic regression analysis indicated that patients with spontaneous HY regression usually had low SFU and APD grades. Furthermore, the rate of surgery was increased in the group of patients with high SFU or APD grades, and these two systems were identified as independent predictors for the requirement of surgery by Kaplan-Meier analysis. Patients with pathological HY had high SFU and APD grades, and these two grading systems may be used as reliable predictors for the outcome of fetal HY, including HY regression, and post-partum surgery.

As traditional molecular imaging modalities, the nature and physical fundamentals of MRI, US, OI, radionuclide-based PET/SPECT imaging, X-ray, and CT are elucidated in this chapter. The philosophy for the design, fabrication, and application of representative imaging probes are also described. Meanwhile, advanced imaging modalities and hybrid imaging probes for both clinical and basic study uses are also introduced to present a clear understanding to a broad and interdisciplinary readership especially at the frontiers of molecular imaging research.