Synthesis and Investigation of a Radioiodinated F3 Peptide Analog as a SPECT Tumor Imaging Radioligand

A radioiodinated derivative of the tumor-homing F3 peptide, (N-(2-{3-[125I]Iodobenzoyl}aminoethyl)maleimide-F3Cys peptide, [125I]IBMF3 was developed for investigation as a SPECT tumor imaging radioligand. For this purpose, we custom synthesized a modified F3 peptide analog (F3Cys) incorporating a C-terminal cysteine residue for site-specific attachment of a radioiodinated maleimide conjugating group. Initial proof-of-concept Fluorescence studies conducted with AlexaFluor 532 C5 maleimide-labeled F3Cys showed distinct membrane and nuclear localization of F3Cys in MDA-MB-435 cells. Additionally, F3Cys conjugated with NIR fluorochrome AlexaFluor 647 C2 maleimide demonstrated high tumor specific uptake in melanoma cancer MDA-MB-435 and lung cancer A549 xenografts in nude mice whereas a similarly labeled control peptide did not show any tumor uptake. These results were also confirmed by ex vivo tissue analysis. No-carrier-added [125I]IBMF3 was synthesized by a radioiododestannylation approach in 73% overall radiochemical yield. In vitro cell uptake studies conducted with [125I]IBMF3 displayed a 5-fold increase in its cell uptake at 4 h when compared to controls. SPECT imaging studies with [125I]IBMF3 in tumor bearing nude mice showed clear visualization of MDA-MB-435 xenografts on systemic administration. These studies demonstrate a potential utility of F3 peptide-based radioligands for tumor imaging with PET or SPECT techniques

Routine computed tomography screening of the chest in high-risk cardiac transplant recipients may improve survival

25th Annual Meeting of the International-Society-of-Heart-and-Lung-Transplantation -- APR 06-09, 2005 -- Philadelphia, PAWOS: 000234308700006PubMed: 16364847Background: Multiple studies have demonstrated an increased incidence of lung cancer in the heart transplant population. We reviewed our cardiac transplantation experience with respect to the development of bronchogenic carcinoma and explored the role of routine chest computed tomography (CT) in its surveillance. Methods: We performed a review of our cardiac transplantation experience, highlighting the incidence of lung cancer, and we analyzed our recent experience with screening chest CT in lung cancer surveillance in this patient group. Results: Eighteen patients developed 20 cases of bronchogenic carcinoma for an incidence of 6.83%. In 10 cases, the patients underwent surgical resection; however, in the remaining cases, the patients were either treated with chemotherapy and/or radiation or they died before initiation of therapy. The actuarial 1-, 2- and 5-year overall survival rates were 49%, 29% and 13%, respectively. The median survival of patients who underwent surgical resection was 28 months (3 to 85 months), whereas the median survival of patients who were either ineligible for surgery or died before initiation of treatment was only 1 month (1 to 13 months). All patients diagnosed with lung cancer by chest CT underwent surgical resection; however, only 37.5% of patients diagnosed with lung cancer by chest X-ray were found at,in appropriate stage for resection (p = 0.025). Conclusions: Cardiac transplant recipients have a significant risk of developing bronchogenic carcinoma. Routine chest CT screening in high-risk patients may enable clinicians to identify disease earlier, which is essential for the option of surgical resection and, therefore, prolonged survival.Int Soc Heart & Lung TransplantatNIGMS NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [5T32GM08593

Contemporary assessment of laryngotracheal trauma

WOS: 000231069700029PubMed: 16077408Objectives: Laryngotracheal trauma is a rare and potentially deadly spectrum of injuries. We sought to characterize the contemporary mechanisms, diagnostic modalities, and outcomes common in laryngotracheal trauma today. Methods: We performed a retrospective analysis of all laryngotracheal trauma cases at 2 major metropolitan hospitals between 1996 and 2004, detailing mechanisms, associated injuries, diagnostic modalities, and outcomes of laryngotracheal trauma. Results: We identified 71 patients with a mean age of 32.8 +/- 13.3 years (range, 15-71 years). In our series penetrating trauma was the cause in 73.2% of patients; however, blunt trauma had a significantly higher mortality (63.2% vs 13.5%, respectively; P < .0001). Blunt mechanisms involved older patients (38.5 +/- 15.2 years vs 30.1 +/- 11.9 years, P = .017), and these patients were more likely to require emergency airways than those with penetrating trauma (78.9% vs 46.2%, P = .017). The requirement of an emergency airway was an independent predictor of mortality (P = .0066). Conclusion: Laryngotracheal trauma is a deadly spectrum of injuries with a mortality of 26.8%. Blunt mechanisms are decreasing in frequency. This might reflect improvements in automobile safety. Additionally, violent crime is on the increase, producing penetrating injuries with increasing frequency. The most fundamental intervention for patients with laryngotracheal injury is airway control. Either routine intubation or a tracheostomy can secure the airway. Blunt trauma and the requirement of an emergency airway are independent predictors of mortality. Laryngotracheal trauma requires prompt recognition, airway protection, and skillful management to lessen the mortality of this deadly spectrum of injuries.NIGMS NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [5T32GM08593

The tyrosine-kinase inhibitor sunitinib targets vascular endothelial (VE)-cadherin: a marker of response to antitumoural treatment in metastatic renal cell carcinoma

International audienceVascular endothelial (VE)-cadherin is an endothelial cell-specific protein responsible for endothelium integrity. Its adhesive properties are regulated by post-translational processing, such as tyrosine phosphorylation at site Y685 in its cytoplasmic domain, and cleavage of its extracellular domain (sVE). In hormone-refractory metastatic breast cancer, we recently demonstrated that sVE levels correlate to poor survival. In the present study, we determine whether kidney cancer therapies had an effect on VE-cadherin structural modifications and their clinical interest to monitor patient outcome