báo cáo hóa học: Physiologic upper limit of pore size in the blood-tumor barrier of malignant solid tumors

Tuyển tập các báo cáo nghiên cứu về hóa học được đăng trên tạp chí sinh học quốc tế đề tài : Physiologic upper limit of pore size in the blood-tumor barrier of malignant solid tumors
Nội dung trích xuất từ tài liệu:
báo cáo hóa học:" Physiologic upper limit of pore size in the blood-tumor barrier of malignant solid tumors"Journal of Translational Medicine BioMed Central Open AccessResearchPhysiologic upper limit of pore size in the blood-tumor barrier ofmalignant solid tumorsHemant Sarin*1,2, Ariel S Kanevsky2, Haitao Wu3, Alioscka A Sousa1,Colin M Wilson3, Maria A Aronova1, Gary L Griffiths3, Richard D Leapman1and Howard Q Vo1,2Address: 1National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892, USA,2Radiology and Imaging Sciences Program, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA and 3Imaging ProbeDevelopment Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USAEmail: Hemant Sarin* - sarinh@mail.nih.gov; Ariel S Kanevsky - kanevskya@mail.nih.gov; Haitao Wu - wuh3@mail.nih.gov;Alioscka A Sousa - sousaali@mail.nih.gov; Colin M Wilson - wilsoncm@mail.nih.gov; Maria A Aronova - aronovaa@mail.nih.gov;Gary L Griffiths - griffithsgl@mail.nih.gov; Richard D Leapman - leapmanr@mail.nih.gov; Howard Q Vo - voho@mail.nih.gov* Corresponding authorPublished: 23 June 2009 Received: 27 April 2009 Accepted: 23 June 2009Journal of Translational Medicine 2009, 7:51 doi:10.1186/1479-5876-7-51This article is available from: http://www.translational-medicine.com/content/7/1/51© 2009 Sarin et al; licensee BioMed Central Ltd.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: The existence of large pores in the blood-tumor barrier (BTB) of malignant solid tumor microvasculature makes the blood-tumor barrier more permeable to macromolecules than the endothelial barrier of most normal tissue microvasculature. The BTB of malignant solid tumors growing outside the brain, in peripheral tissues, is more permeable than that of similar tumors growing inside the brain. This has been previously attributed to the larger anatomic sizes of the pores within the BTB of peripheral tumors. Since in the physiological state in vivo a fibrous glycocalyx layer coats the pores of the BTB, it is possible that the effective physiologic pore size in the BTB of brain tumors and peripheral tumors is similar. If this were the case, then the higher permeability of the BTB of peripheral tumor would be attributable to the presence of a greater number of pores in the BTB of peripheral tumors. In this study, we probed in vivo the upper limit of pore size in the BTB of rodent malignant gliomas grown inside the brain, the orthotopic site, as well as outside the brain in temporalis skeletal muscle, the ectopic site. Methods: Generation 5 (G5) through generation 8 (G8) polyamidoamine dendrimers were labeled with gadolinium (Gd)-diethyltriaminepentaacetic acid, an anionic MRI contrast agent. The respective Gd-dendrimer generations were visualized in vitro by scanning transmission electron microscopy. Following intravenous infusion of the respective Gd-dendrimer generations (Gd-G5, N = 6; Gd-G6, N = 6; Gd-G7, N = 5; Gd-G8, N = 5) the blood and tumor tissue pharmacokinetics of the Gd-dendrimer generations were visualized in vivo over 600 to 700 minutes by dynamic contrast-enhanced MRI. One additional animal was imaged in each Gd-dendrimer generation group for 175 minutes under continuous anesthesia for the creation of voxel-by-voxel Gd concentration maps. Results: The estimated diameters of Gd-G7 dendrimers were 11 ± 1 nm and those of Gd-G8 dendrimers were 13 ± 1 nm. The BTB of ectopic RG-2 gliomas was more permeable than the BTB Page 1 of 13 (page number not for citation purposes)Jo ...