Synthesis, radiolabeling and quality control of 111In-DOTA-bevacizumab for radioimmunoscintigraphy of VEGF receptors

2013 ◽  
Vol 101 (9) ◽  
pp. 577-584
Author(s):  
A. Khorami-Moghadam ◽  
A. R. Jalilian ◽  
K. Yavari ◽  
B. Alirezapour ◽  
M. Mazidi ◽  
...  
Keyword(s):  
Radiochemical Purity ◽  
Human Colon ◽  
Vascular Endothelial ◽  
Tumor Uptake ◽  
Wild Type ◽  
Human Colon Cancer ◽  
Biodistribution Studies ◽  
Endothelial Growth Factor

Summary In this study, bevacizumab was successively labeled with 111In-InCl3 after conjugation with DOTA-NHS-ester followed by molecular filtration and determination of the average number ofDOTAconjugated per mAb (6 : 1) by spectrophotometric method. Radiochemical purity (> 97%, measured by ITLC and HPLC), integrity of protein after radiolabeling (gel electrophoresis) and stability of 111In-DOTA-Bevacizumab (in final formulation, human serum, liver/kidney homogenates) were determined in 24-72 h as well as biodistribution studies in wild-type rats and human colon cancer (SW-480) bearing mice. The accumulation of the radiolabeled antibody was consistent with the former reported Bevacizumab conjugates. Significant tumor uptake (8%) was observed at 72 h p.i. Tumor/muscle uptake ratios were 2.6 (24 h), 9.74 (48 h) and 25 (72 h). 111In- DOTA-Bevacizumab was prepared as a SPECT molecular imaging agent for diagnosis and follow-up of vascular endothelial growth factor A (VEGF-A) expression in oncology.

scholarly journals P1001RENAL DAMAGE ASSOCIATED WITH INTRAVITREAL ADMINISTRATION OF ANTI-VEGF DRUGS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Maria Fernandez-Vidal ◽  
Candela Moliz ◽  
Beatriz Redondo ◽  
Teresa Bada Bosch ◽  
Lucia Aubert ◽  
...  
Keyword(s):  
Renal Function ◽  
Diabetic Patients ◽  
Vascular Endothelial ◽  
Median Dose ◽  
Anti Vegf ◽  
Group 2 ◽  
Endothelial Growth Factor ◽  
Group 1

Abstract Background and Aims Vascular endothelial growth factor inhibitors (anti-VEGF) have been shown to be effective in the treatment of macular degeneration and diabetic macular edema. It is known that systemic administration of these drugs can produce adverse renal effects, such as decreased glomerular filtration rate (eFGR), proteinuria, hypertension or thrombotic microangiopathy. However, there is little information about it when the administration is intravitreal. The aim of this study was analyzed the effect of anti-VEGF drugs on renal function and proteinuria. Method Observational and prospective study on diabetic patients, which were divided into two groups: non-cronic kidney disease (CKD) (group 1) and CKD (group 2). We analyzed clinical and analytical variables during follow-up. Results We included 45 diabetic patients (55.6% males) with a median age of 75 (50-91) years. Forty one patients (91.1%) were hypertensive and thirty three (73.3%) were CKD patients. Twenty six (57.8%) received bevazicumab, while the rest (42.2%) received ranibizumab, with a median dose of 6 (1-22). The median follow-up was 25 (9-94) months. The evolution of eFGR and albuminuria are described in Figure 1, where it stands out the increase in albuminuria in group 2. Regarding the drug type, there were no differences. Within the CKD group, one patient presented two episodes of decompensation of heart failure after the administration of an anti-VEGF drug, and two required the initiation of renal replacement therapy. Conclusion Based on the results of our cohort, we believe that it would be advisable to establish a closer monitoring in diabetic patients who are administered an intravitreal anti-VEGF drug, with determination of renal function as well as albuminuria to establish an early diagnosis of possible complications.

scholarly journals Aldose Reductase Inhibition Prevents Hypoxia-induced Increase in Hypoxia-inducible Factor-1α (HIF-1α) and Vascular Endothelial Growth Factor (VEGF) by Regulating 26 S Proteasome-mediated Protein Degradation in Human Colon Cancer Cells

2011 ◽  
Vol 286 (27) ◽  
pp. 24089-24100 ◽  
Author(s):  
Ravinder Tammali ◽  
Ashish Saxena ◽  
Satish K. Srivastava ◽  
Kota V. Ramana
Keyword(s):  
Colon Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Cancer Cells ◽  
Lysyl Oxidase ◽  
Human Colon ◽  
Vascular Endothelial ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Endothelial Growth Factor ◽  
Human Colon Cancer Cells

The development of intratumoral hypoxia, a hallmark of rapidly progressing solid tumors, renders tumor cells resistant to chemotherapy and radiation therapy. We have recently shown that inhibition of aldose reductase (AR), an enzyme that catalyzes the reduction of lipid aldehydes and their glutathione conjugates, prevents human colon cancer cell growth in culture as well as in nude mouse xenografts by inhibiting the NF-κB-dependent activation of oxidative stress-mediated inflammatory and carcinogenic markers. However, the role of AR in mediating hypoxic stress signals is not known. We therefore investigated the molecular mechanisms by which AR inhibition prevents the hypoxia-induced human colon cancer cells growth and invasion. Our results indicate that AR inhibition by the pharmacological inhibitor fidarestat or ablation by AR-specific siRNA prevents hypoxia-induced proliferation of HT29, SW480, and Caco-2 colon cancer cells. Furthermore, hypoxia-induced increase in the level of HIF-1α in colon cancer cells was significantly decreased by AR inhibition. During hypoxic conditions, treatment of HT29 cells with the AR inhibitor fidarestat significantly decreased the expression of vascular endothelial growth factor, a down target of HIF-1α, at both mRNA and protein levels and also prevented the activation of PI3K/AKT, GSK3β, Snail, and lysyl oxidase. Furthermore, inhibition of hypoxia-induced HIF-1α protein accumulation by AR inhibition was abolished in the presence of MG132, a potent inhibitor of the 26 S proteasome. In addition, AR inhibition also prevented the hypoxia-induced inflammatory molecules such as Cox-2 and PGE2 and expression of extracellular matrix proteins such as MMP2, vimentin, uPAR, and lysyl oxidase 2. In conclusion, our results indicate that AR mediates hypoxic signals, leading to tumor progression and invasion.

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