Magnetic Resonance Macromolecular Agents for Monitoring Tumor Microvessels and Angiogenesis Inhibition

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using macromolecular contrast media enables assessments of the tumor vasculature based on the differential distribution of the contrast agent within normal and pathologic tissues. Quantitative assays of both morphologic and functional properties can provide useful diagnostic insight into tissue angiogenesis. The use of MRI enhanced with macromolecular agents for the characterization of tumor microvessels has been experimentally demonstrated in a range of malignant tumor types. Kinetic analysis of DCE-MRI data can be used to estimate microvascular permeability and tumor blood volume. By measuring these functional tumor properties, an accurate, noninvasive, and quantitative description of the microcirculation of individual tumors can be acquired, improving the specificity of imaging examinations for cancer diagnosis and for treatment and follow up. The noninvasive MRI assessment of tumor angiogenesis can be applied in the diagnostic differentiation between benign and malignant tumors and can also provide means for in vivo monitoring of antitumor therapy. In this review, the potential clinical applications and limitations of various macromolecular contrast agents applied for evaluations of tumor angiogenesis, with and without drug interventions, are discussed.

[1]  E. Kahn,et al.  Assessing perfusion and capillary permeability changes induced by a VEGF inhibitor in human tumor xenografts using macromolecular MR imaging contrast media. , 2002, Academic radiology.

[2]  Andrea Sbarbati,et al.  Effect of Tamoxifen in an Experimental Model of Breast Tumor Studied by Dynamic Contrast-Enhanced Magnetic Resonance Imaging and Different Contrast Agents , 2005, Investigative radiology.

[3]  M. Port,et al.  P792: a rapid clearance blood pool agent for magnetic resonance imaging: preliminary results , 2001, Magnetic Resonance Materials in Physics, Biology and Medicine.

[4]  R W Günther,et al.  Differentiation of spontaneous canine breast tumors using dynamic magnetic resonance imaging with 24-Gadolinium-DTPA-cascade-polymer, a new blood-pool agent. Preliminary experience. , 1996, Investigative radiology.

[5]  Georg Breier,et al.  Molecular Mechanisms of Developmental and Tumor Angiogenesis , 1994, Brain pathology.

[6]  R. Dolan,et al.  MS-325: albumin-targeted contrast agent for MR angiography. , 1998, Radiology.

[7]  G. Frija,et al.  Superparamagnetic iron oxides as positive MR contrast agents: in vitro and in vivo evidence. , 1993, Magnetic resonance imaging.

[8]  Robert C. Brasch,et al.  MRI monitoring of tumor response following angiogenesis inhibition in an experimental human breast cancer model , 2003, European Journal of Nuclear Medicine and Molecular Imaging.

[9]  G. Adam,et al.  Gd‐DTPA‐cascade‐polymer: Potential blood pool contrast agent for MR imaging , 1994, Journal of magnetic resonance imaging : JMRI.

[10]  G. Adam,et al.  Dynamic contrast‐enhanced MR imaging of the upper abdomen: Enhancement properties of gadobutrol, gadolinium‐DTPA‐polylysine, and gadolinium‐DTPA‐cascade‐polymer , 1994, Magnetic resonance in medicine.

[11]  D M Shames,et al.  Comparison of Gadomer-17 and gadopentetate dimeglumine for differentiation of benign from malignant breast tumors with MR imaging. , 2000, Academic radiology.

[12]  N. van Bruggen,et al.  Magnetic resonance imaging detects suppression of tumor vascular permeability after administration of antibody to vascular endothelial growth factor. , 1998, Cancer investigation.

[13]  A. Padhani MRI for assessing antivascular cancer treatments. , 2003, The British journal of radiology.

[14]  T. Helbich,et al.  Prostate cancer tumor grade differentiation with dynamic contrast-enhanced MR imaging in the rat: comparison of macromolecular and small-molecular contrast media--preliminary experience. , 1999, Radiology.

[15]  D M Shames,et al.  A MRI spatial mapping technique for microvascular permeability and tissue blood volume based on macromolecular contrast agent distribution , 1997, Magnetic resonance in medicine.

[16]  C. Corot,et al.  Comparison of plasma and peritoneal concentrations of various categories of MRI blood pool agents in a murine experimental pharmacokinetic model , 2001, Magnetic Resonance Materials in Physics, Biology and Medicine.

[17]  M. Hynes,et al.  Development of a novel nonaromatic small-molecule MR contrast agent for the blood pool. , 1998, Academic radiology.

[18]  R. Brasch,et al.  MRI monitoring of Avastin™ antiangiogenesis therapy using B22956/1, a new blood pool contrast agent, in an experimental model of human cancer , 2004, Journal of magnetic resonance imaging : JMRI.

[19]  H. Schlemmer,et al.  Dynamic Magnetic Resonance Tomography and Proton Magnetic Resonance Spectroscopy of Prostate Cancers in Rats Treated by Radiotherapy , 2004, Investigative radiology.

[20]  Viktor Novikov,et al.  Tumor microvascular changes in antiangiogenic treatment: Assessment by magnetic resonance contrast media of different molecular weights , 2004, Journal of magnetic resonance imaging : JMRI.

[21]  R. Brasch,et al.  Contrast-Enhanced Magnetic Resonance Imaging Estimation of Altered Capillary Permeability in Experimental Mammary Carcinomas After X-Irradiation , 1994, Investigative radiology.

[22]  D M Shames,et al.  Quantification of the extraction fraction for gadopentetate across breast cancer capillaries , 1998, Magnetic resonance in medicine.

[23]  P M Carpenter,et al.  Characterization of N‐ethyl‐N‐nitrosourea‐induced malignant and benign breast tumors in rats by using three MR contrast agents , 1999, Journal of magnetic resonance imaging : JMRI.

[24]  H. Weinmann,et al.  In vivo and in vitro evaluation of Gd-DTPA-polylysine as a macromolecular contrast agent for magnetic resonance imaging. , 1991, Investigative radiology.

[25]  R. Brasch,et al.  Tumor microvascular characterization using ultrasmall superparamagnetic iron oxide particles (USPIO) in an experimental breast cancer model , 2001, Journal of magnetic resonance imaging : JMRI.

[26]  T. Helbich,et al.  A new polysaccharide macromolecular contrast agent for MR imaging: Biodistribution and imaging characteristics , 2000, Journal of magnetic resonance imaging : JMRI.

[27]  J. Finn,et al.  Three‐dimensional MR pulmonary perfusion imaging and angiography with an injection of a new blood pool contrast agent B‐22956/1 , 2001, Journal of magnetic resonance imaging : JMRI.

[28]  R. Brasch,et al.  MRI characterization of tumors and grading angiogenesis using macromolecular contrast media: status report. , 2000, European journal of radiology.

[29]  R. Brasch New directions in the development of MR imaging contrast media. , 1992, Radiology.

[30]  C. Corot,et al.  Physical, chemical and biological evaluations of CMD-A2-Gd-DOTA. A new paramagnetic dextran polymer. , 1997, Acta radiologica. Supplementum.

[31]  S. H. Koenig,et al.  1H-NMRD and17O-NMR assessment of water exchange and rotational dynamics of two potential MRI agents: MP-1177 (an extracellular agent) and MP-2269 (a blood pool agent) , 1999, Magnetic Resonance Materials in Physics, Biology and Medicine.

[32]  D M Shames,et al.  MR imaging characterization of microvessels in experimental breast tumors by using a particulate contrast agent with histopathologic correlation. , 2001, Radiology.

[33]  D M Shames,et al.  Measurement of capillary permeability to macromolecules by dynamic magnetic resonance imaging: A quantitative noninvasive technique , 1993, Magnetic resonance in medicine.

[34]  D. Hanahan,et al.  Patterns and Emerging Mechanisms of the Angiogenic Switch during Tumorigenesis , 1996, Cell.

[35]  N Grenier,et al.  Evaluation of Intrarenal Distribution of Ultrasmall Superparamagnetic Iron Oxide Particles by Magnetic Resonance Imaging and Modification by Furosemide and Water Restriction , 1994, Investigative radiology.

[36]  M. Ogan,et al.  Albumin labeled with Gd-DTPA: an intravascular contrast-enhancing agent for magnetic resonance blood pool imaging: preparation and characterization. , 1987, Investigative radiology.

[37]  P. Anelli,et al.  Gadocoletic Acid Trisodium Salt (B22956/1): A New Blood Pool Magnetic Resonance Contrast Agent With Application in Coronary Angiography , 2006, Investigative radiology.

[38]  Wolfgang Ebert,et al.  Pharmacokinetics of Gadomer-17, a new dendritic magnetic resonance contrast agent , 2001, Magnetic Resonance Materials in Physics, Biology and Medicine.

[39]  Xiaobing Fan,et al.  New model for analysis of dynamic contrast‐enhanced MRI data distinguishes metastatic from nonmetastatic transplanted rodent prostate tumors , 2004, Magnetic resonance in medicine.

[40]  T. Helbich,et al.  MRI assessment of microvascular characteristics in experimental breast tumors using a new blood pool contrast agent (MS‐325) with correlations to histopathology , 2001, Journal of magnetic resonance imaging : JMRI.

[41]  Atle Bjørnerud,et al.  Quantification of breast tumor microvascular permeability with feruglose-enhanced MR imaging: initial phase II multicenter trial. , 2003, Radiology.

[42]  R. Lauffer,et al.  Preclinical evaluation of the pharmacokinetics, biodistribution, and elimination of MS-325, a blood pool agent for magnetic resonance imaging. , 1997, Investigative radiology.

[43]  O Nalcioglu,et al.  Tumor characterization with dynamic contrast–enhanced MRI using mr contrast agents of various molecular weights , 1998, Magnetic resonance in medicine.

[44]  D M Shames,et al.  Magnetic resonance imaging in an experimental model of human ovarian cancer demonstrating altered microvascular permeability after inhibition of vascular endothelial growth factor. , 2000, American journal of obstetrics and gynecology.

[45]  T. Roberts,et al.  Physiologic measurements by contrast‐enhanced MR imaging: Expectations and limitations , 1997, Journal of magnetic resonance imaging : JMRI.

[46]  N. van Bruggen,et al.  Assessing tumor angiogenesis using macromolecular MR imaging contrast media , 1997, Journal of magnetic resonance imaging : JMRI.

[47]  I. Zuna,et al.  Evaluation of neoadjuvant chemotherapeutic response of breast cancer using dynamic MRI with high temporal resolution , 2002, European Radiology.

[48]  M. Hynes,et al.  Synthesis and preliminary evaluation of MP‐2269: A novel, nonaromatic small‐molecule blood‐pool MR contrast agent , 1998, Magnetic resonance in medicine.

[49]  V. Deshpande,et al.  Comparison of Gradient-Echo and Steady-State Free Precession for Coronary Artery Magnetic Resonance Angiography Using a Gadolinium-Based Intravascular Contrast Agent , 2006, Investigative radiology.

[50]  R. Brasch,et al.  Contrast-enhanced MR imaging assessment of tumor capillary permeability: effect of irradiation on delivery of chemotherapy. , 1996, Radiology.

[51]  Hon J. Yu,et al.  Measurement of Volumetric and Vascular Changes with Dynamic Contrast Enhanced MRI for Cancer Therapy Monitoring , 2002, Technology in cancer research & treatment.

[52]  Robert C. Brasch,et al.  Macromolecular contrast agents for MR mammography: current status , 2003, European Radiology.

[53]  A Heerschap,et al.  Fast dynamic gadolinium‐enhanced MR imaging of urinary bladder and prostate cancer , 1999, Journal of magnetic resonance imaging : JMRI.

[54]  U Schmiedl,et al.  Albumin labeled with Gd-DTPA as an intravascular, blood pool-enhancing agent for MR imaging: biodistribution and imaging studies. , 1987, Radiology.

[55]  M. Moseley,et al.  Comparison of the contrast-enhancing properties of albumin-(Gd-DTPA) and Gd-DTPA at 2.0 T: and experimental study in rats. , 1986, AJR. American journal of roentgenology.

[56]  O. Haraldseth,et al.  New intravascular contrast agent applied to dynamic contrast enhanced MR imaging of human breast cancer. , 2003, Acta radiologica.

[57]  J. Hoffman,et al.  Tumor angiogenesis: molecular pathology, therapeutic targeting, and imaging. , 2000 .

[58]  D P Dearnaley,et al.  Dynamic contrast enhanced MRI of prostate cancer: correlation with morphology and tumour stage, histological grade and PSA. , 2000, Clinical radiology.

[59]  R. Brasch,et al.  AUR Memorial Award 1991. Immunogenicity of gadolinium-based contrast agents for magnetic resonance imaging. Induction and characterization of antibodies in animals. , 1991, Investigative radiology.

[60]  D C Peters,et al.  Steady-state and dynamic MR angiography with MS-325: initial experience in humans. , 1998, Radiology.

[61]  O Nalcioglu,et al.  Investigation of longitudinal vascular changes in control and chemotherapy‐treated tumors to serve as therapeutic efficacy predictors , 1999, Journal of magnetic resonance imaging : JMRI.

[62]  Peter Caravan,et al.  Species Dependence on Plasma Protein Binding and Relaxivity of the Gadolinium-Based MRI Contrast Agent MS-325 , 2006, Investigative radiology.

[63]  R. Dolan,et al.  First-pass renal perfusion imaging using MS-325, an albumin-targeted MRI contrast agent. , 1999, Investigative radiology.

[64]  G Brix,et al.  Multicompartment analysis of gadolinium chelate kinetics: Blood‐tissue exchange in mammary tumors as monitored by dynamic MR imaging , 1999, Journal of magnetic resonance imaging : JMRI.

[65]  R K Jain,et al.  Vascular permeability in a human tumor xenograft: molecular size dependence and cutoff size. , 1995, Cancer research.

[66]  D M Shames,et al.  Assessment of a rapid clearance blood pool MR contrast medium (P792) for assays of microvascular characteristics in experimental breast tumors with correlations to histopathology , 2001, Magnetic resonance in medicine.

[67]  T. Woolsey,et al.  Albumin‐binding MR blood pool agents as MRI contrast agents in an intracranial mouse glioma model , 2003, Magnetic resonance in medicine.

[68]  Angiogenesis imaging. , 2000, Academic radiology.

[69]  R. Brasch,et al.  Characteristics of gadolinium-DTPA complex: a potential NMR contrast agent. , 1984, AJR. American journal of roentgenology.

[70]  D M Shames,et al.  Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media. , 1998, AJR. American journal of roentgenology.