High levels of GRPR were observed in prostate and breast tissues during malignant transformation 3, 4. In contrast, GPPR has very limited expression in normal prostate 4. Elevated GRPR expression was found on the cell membrane of prostatic intraepithelial neoplasia, primary prostate cancer, invasive prostatic carcinoma, and androgen-independent human cancer cells as well as well-differentiated and metastatic prostate cancers 4. GRPR was reported to be overexpressed on the surfaces of various human cancers, including breast, colon, lung, and prostate cancer 3, 4, 5. Thus, there is an urgent need to develop sensitive and accurate non-invasive imaging methods to assess cancer states in vivo using biomarkers, and subsequently monitor tumor progression, metastasis, and treatment effectiveness with high specificity.Д«iomarkers, such as gastrin-releasing peptide (GRP) receptor (GRPR), were suggested to be attractive early cancer indicators 1, 2. Similarly, lung cancer lacks an accurate and non-invasive detection method, despite being the leading cause of cancer related death in men and women in the United States, with 86,740 deaths in men and 70,759 in women in 2012. Current determination of the histological type of prostate cancer by invasive clinical diagnostic procedures, e.g., biopsy, may only be achieved several years after the initial finding of elevated levels of prostate-specific antigen (PSA) due to limitations of existing imaging methodologies for non-invasive assessment of the tumor. One of the major reasons for the high mortality is the limitations of current methods for the early detection, accurate diagnosis, and treatment monitoring capabilities of this disease. According to the estimation from the National Cancer Institute, about 240,890 new cases occurred in 2011, with 33,720 associated deaths. Prostate cancer is the leading cause of tumor-related death in men in the Western world. ProCA1.GRPR is expected to have important preclinical and clinical implications for the early detection of cancer and for monitoring treatment effects. ProCA1.GRPR enables in vivo detection of GRPR expression and spatial distribution in both PC3 and H441 tumors in mice using MRI. In addition to its strong binding affinity for GRPR (K dвЂ‰=вЂ‰2.7вЂ‰nM), ProCA1.GRPR has high relaxivity (r 1вЂ‰=вЂ‰42.0вЂ‰mM в€’1s в€’1 at 1.5вЂ‰T and 25вЂ‰вЊ) and strong Gd 3+ selectivity over physiological metal ions. Here, we report the development of a GRPR-targeted MRI contrast agent by grafting the GRPR targeting moiety into a scaffold protein with a designed Gd 3+ binding site (ProCA1.GRPR). However, monitoring temporal and spatial expression of GRPR in vivo by clinical MRI is severely hampered by the lack of contrast agents with high relaxivity, targeting capability and tumor penetration. The degree of charge of the contrast agents used in the present study did not result in alteration of the prolonged blood pooling time.Gastrin-releasing peptide receptor (GRPR) is differentially expressed on the surfaces of various diseased cells, including prostate and lung cancer. Taken together, all three differentlyвЂ‘charged CMEADM2 particles exhibited prolonged vascular enhancing effects, compared with the USPIO. No significant differences were attributable to the electric charge among the CMEADMвЂ‘, CMEADM2вЂ‘ or and CMEADM+ particles when analyzed with analysis of variance and Tukey's HSD test. Following injection with the CMEADMs, but not with USPIO, the in vivo pooling time was prolonged to >300 min. The relative signal intensity (SIrel) of each was calculated using the following formula: SIrel = (SI postвЂ‘contrast вЂ‘ SI preвЂ‘contrast / SI preвЂ‘contrast) x 100. The evaluation was performed by injecting four groups of three Japanese white rabbits each with CMEADMвЂ‘, CMEADM2вЂ‘, CMEADM+ (surface charges: вЂ‘10.4, вЂ‘41.0 and +9.6 mV, respectively) or with ultrasmall superparamagnetic iron oxide (USPIO вЂ‘11.5 mV). The present study evaluated whether the degree of charge alters the bloodвЂ‘pooling time. CMEADM particles carry a negative or positive charge due to the binding of amino and carboxyl groups to the hydroxyl group of dextran. As gadolinium (Gd)-based agents may increase the risk for nephrogenic systemic fibrosis in patients with severe renal insufficiency, the present study synthesized carboxymethyl-diethylaminoethyl dextran magnetite (CMEADM) particles as a blood-pooling, non-GdвЂ‘based contrast agent. Gadofosveset trisodium is available as a prolonged pooling vascular contrast agent for magnetic resonance imaging.

Dextran mr contrast