Synthesis of hydrophilic HYNIC-[1,2,4,5]tetrazine conjugates and their use in antibody pretargeting with 99mTc.

Pretargeted imaging, based on the highly reactive process between [1,2,4,5]tetrazines with trans-cyclooctene (TCO), appears as an attractive strategy to overcome disadvantages associated with traditional radioimmunoconjugates. To be successful, the radiolabeled component should react in vivo with the conjugated antibody and the non reactive excess clear fast from the organism. Herein, we explore the in vivo effects of hydrophilic linker incorporation into [1,2,4,5]tetrazine systems bearing a 6-hydrazinonicotinyl (HYNIC) moiety for technetium-99m coordination. Incorporation of a polypeptide chain containing hydrophilic aminoacids, resulted in a derivative with renal clearance. Pretargeted bevacizumab imaging was used as proof of concept.

Serum albumin and vascular endothelial growth factor in epithelial ovarian cancer: looking at adnexal tumor drainage.

PURPOSE: This study aims to analyze serum albumin levels (SAL) in relation to concentrations of vascular endothelial growth factor (VEGF) from peripheral plasma, infundibular plasma, peritoneal fluids and the peritoneal burden of VEGF of patients with epithelial ovarian cancer. METHODS: Exploratory analyses of SAL in 39 patients and its relation to mean concentrations of VEGF from the origins are described above. Statistical analyses comprised Student's t test, Mann-Whitney test and Pearson's and Spearman's correlation coefficient. RESULTS: Both infundibular concentrations of VEGF and the peritoneal burden of VEGF showed significant differences between SAL dichotomized at 3 g/dl. Concentrations of VEGF in peritoneal fluids were not significant in relation to SAL. Peripheral plasma VEGF levels did not show any linear correlation with SAL. Indeed, SAL showed a significant negative linear correlation (p < 0.001) to infundibular plasma as well as the peritoneal burden of VEGF (p = 0.004). CONCLUSIONS: Infundibular mean concentrations of VEGF may contribute to reduce SAL in advanced staging rather than the peripheral plasma concentrations of this glycoprotein. The peritoneal burden of VEGF may also aid in decreasing levels of serum albumin.

Peritoneal VEGF burden as a predictor of cytoreductive surgery outcome in women with epithelial ovarian cancer.

OBJECTIVE: To determine whether peripheral plasma concentration, peritoneal fluid concentration, and/or peritoneal vascular endothelial growth factor (VEGF) burden can predict the possibility of optimal cytoreduction in women with epithelial ovarian carcinoma (EOC); and if so, to determine cutoff values below which optimal cytoreduction is likely to occur. METHODS: We measured plasma VEGF concentration, peritoneal VEGF concentration, and VEGF burden in 46 women undergoing cytoreductive surgery. Univariate analysis, bivariate analysis, correlation tests, and stepwise regression were performed with cytoreduction as the outcome. RESULTS: The VEGF burden best predicted the outcome. The area under the curve was 0.84 and the log-transformed cutoff value was 15.52 log pg. Overall, the chance of optimal cytoreduction was 11 times greater when the VEGF burden was less than 15.52 log pg. For women with advanced disease, the chance was 6 times greater below this value. CONCLUSION: The VEGF burden may quantify tumor activity, and it could be used when selecting patients likely to benefit from induction chemotherapy before undergoing cytoreductive surgery.