Tumor Characterization with Dynamic Contrast Enhanced Magnetic Resonance Imaging and Biodegradable Macromolecular Contrast Agents in Mice
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
To investigate the efficacy of polydisulfide-based biodegradable macromolecular contrast agents of different degradability and molecular weight for tumor characterization based on angiogenesis using dynamic contrast enhanced MRI (DCE-MRI).
Biodegradable macromolecular MRI contrast agents, Gd-DTPA cystamine copolymers (GDCC) and Gd-DTPA cystine copolymers (GDCP), with molecular weight of 20 and 70 KDa were evaluated for tumor characterization. Gd(DTPA-BMA) and a prototype of macromolecular contrast agent, albumin-(Gd-DTPA), were used as controls. The DCE-MRI studies were performed in nude mice bearing MDA PCa 2b and PC-3 human prostate tumor xenografts. Tumor angiogenic kinetic parameters including endothelium transfer coefficient (Ktrans) and fractional tumor plasma volume (fPV) were calculated from the DCE-MRI data using a two-compartment model and compared between the two different tumor models for each contrast agent.
There was no significant difference in the fPV values between two tumor models estimated with the same agent except for GDCC-70. The Ktrans values in both tumor models decreased with the increase of molecular weight of contrast agents. With the same high molecular weight (70 KDa), GDCC-70 showed a higher Ktrans values than GDCP-70 due to high degradability of the former in both tumor models (p < 0.05). The Ktrans values of MDA PCa 2b tumors were significantly higher than those of PC-3 tumors estimated by Gd(DTPA-BMA), GDCC-20, GDCC-70, GDCP-70, and albumin-(Gd-DTPA) (p < 0.05).
The polydisulfide-based biodegradable macromolecular MRI contrast agents are promising in tumor characterization and differentiation with dynamic contrast enhanced MRI.
- Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics. CA Cancer J Clin. 2008;58:71–96 CrossRef
- Gossmann A, Okuhata Y, Shames DM, 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. Radiology. 1999;213:265–72.
- Quinlan DM, Partin AW, Walsh PC. Can aggressive prostatic carcinomas be identified and can their natural history be altered by treatment? Urology. 1995;46:77–82. CrossRef
- Yancopoulos GD, Davis S, Gale NW, Rudge JS, Wiegand SJ, Holash J. Vascular-specific growth factors and blood vessel formation. Nature. 2000;407:242–8. CrossRef
- Ferrara N. VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer. 2002;2:795–803. CrossRef
- Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma. N Engl J Med. 1991;324:1–8.
- Aref M, Chaudhari AR, Bailey KL, Aref S, Wiener EC. Comparison of tumor histology to dynamic contrast enhanced magnetic resonance imaging-based physiological estimates. Magn Reson Imaging. 2008;26:1279–93. CrossRef
- Su MY, et al. Correlation of dynamic contrast enhanced MRI parameters with microvessel density and VEGF for assessment of angiogenesis in breast cancer. J Magn Reson Imaging. 2003;18:467–77. CrossRef
- Fujimoto K, et al. Small peripheral pulmonary carcinomas evaluated with dynamic MR imaging: correlation with tumor vascularity and prognosis. Radiology. 2003;227:786–93. CrossRef
- Raatschen HJ, Simon GH, Fu Y, Sennino B, Shames DM, Wendland MF, et al. Vascular permeability during antiangiogenesis treatment: MR imaging assay Results as biomarker for subsequent tumor growth in rats. Radiology. 2008;247:391–9. CrossRef
- Daldrup H, Shames DM, Wendland M, et al. Correlation of dynamic contrast-enhanced MR imaging with histologic tumor grade: comparison of macromolecular and small-molecular contrast media. AJR Am J Roentgenol. 1998;171:941–9.
- Tofts PS, Brix G, Buckley DL, et al. Estimating kinetic parameters from dynamic contrast-enhanced T(1)-weighted MRI of a diffusable tracer: standardized quantities and symbols. J Magn Reson Imaging. 1999;10:223–32. CrossRef
- Jordan BF, Runquist M, Raghunand N, et al. The thioredoxin-1 inhibitor 1-methylpropyl 2-imidazolyl disulfide (PX-12) decreases vascular permeability in tumor xenografts monitored by dynamic contrast enhanced magnetic resonance imaging. Clin Cancer Res. 2005;11:529–36.
- Padhani AR. Dynamic contrast-enhanced MRI in clinical oncology: current status and future directions. J Magn Reson Imaging. 2002;16:407–22. CrossRef
- Roberts TP, Turetschek K, Preda A, et al. Tumor microvascular changes to anti-angiogenic treatment assessed by MR contrast media of different molecular weights. Acad Radiol. 2002;9:S511–3. CrossRef
- Brasch RC. New directions in the development of MR imaging contrast media. Radiology. 1992;183:1–11.
- van Dijke CF, Brasch RC, Roberts TP, et al. Mammary carcinoma model: correlation of macromolecular contrast-enhanced MR imaging characterizations of tumor microvasculature and histologic capillary density. Radiology. 1996;198:813–8.
- de Lussanet QG, Langereis S, Beets-Tan RG, et al. Dynamic contrast-enhanced MR imaging kinetic parameters and molecular weight of dendritic contrast agents in tumor angiogenesis in mice. Radiology. 2005;235:65–72. CrossRef
- Desser TS, Rubin DL, Muller HH, et al. Dynamics of tumor imaging with Gd-DTPA-polyethylene glycol polymers: dependence on molecular weight. J Magn Reson Imaging. 1994;4:467–72. CrossRef
- Bogdanov AA Jr, Weissleder R, Frank HW, et al. A new macromolecule as a contrast agent for MR angiography: preparation, properties, and animal studies. Radiology. 1993;187:701–6.
- Su MY, Wang Z, Carpenter PM, Lao X, Muhler A, Nalcioglu O. Characterization of N-ethyl-N-nitrosourea-induced malignant and benign breast tumors in rats by using three MR contrast agents. J. Magn. Reson. Imaging. 1999;9:177–86. CrossRef
- Su MY, Muhler A, Lao X, Nalcioglu O. Tumor characterization with dynamic contrast-enhanced MRI using MR contrast agents of various molecular weights. Magn Reson Med. 1998;39:259–69. CrossRef
- Feng Y, Zong Y, Ke T, Jeong EK, Parker DL, Lu ZR. Pharmacokinetics, biodistribution and contrast enhanced MR blood pool imaging of Gd-DTPA cystine copolymers and Gd-DTPA cystine diethyl ester copolymers in a rat model. Pharm Res. 2006;23:1736–42. CrossRef
- Preda A, van Vliet M, Krestin GP, Brasch RC, van Dijke CF. Magnetic resonance macromolecular agents for monitoring tumor microvessels and angiogenesis inhibition. Invest Radiol. 2006;41:325–31. CrossRef
- Lu ZR, Parker DL, Goodrich KC, Wang X, Dalle JG, Buswell HR. Extracellular biodegradable macromolecular gadolinium(III) complexes for MRI. Magn Reson Med. 2004;51:27–34. CrossRef
- Zong Y, Wang X, Goodrich KC, Mohs AM, Parker DL, Lu ZR. Contrast-enhanced MRI with new biodegradable macromolecular Gd(III) complexes in tumor-bearing mice. Magn Reson Med. 2005;53:835–42. CrossRef
- Wang X, Feng Y, Ke T, Schabel M, Lu ZR. Pharmacokinetics and tissue retention of (Gd-DTPA)-cystamine copolymers, a biodegradable macromolecular magnetic resonance imaging contrast agent. Pharm Res. 2005;22:596–602. CrossRef
- Feng Y, Jeong E-K, Mohs A, Emerson L, Lu Z-R. Characterization of tumor angiogenesis with dynamic contrast enhanced magnetic resonance imaging and biodegradable macromolecular contrast agents in mice. Magn Reson Med. 2008;60:1347–52. CrossRef
- Ogan MD, Schmiedl U, Moseley ME, Grodd W, Paajanen H, Brasch RC. Albumin labeled with Gd-DTPA. An intravascular contrast-enhancing agent for magnetic resonance blood pool imaging: preparation and characterization. Invest Radiol. 1987;22:665–71. CrossRef
- Navone NM, Olive M, Ozen M, et al. Establishment of two human prostate cancer cell lines derived from a single bone metastasis. Clin Cancer Res. 1997;3:2493–500.
- Kim YR, Savellano MD, Savellano DH, Weissleder R, Bogdanov A Jr. Measurement of tumor interstitial volume fraction: method and implication for drug delivery. Magn Reson Med. 2004;52:485–94. CrossRef
- Kim YR, Savellano MD, Weissleder R, Bogdanov A Jr. Steady-state and dynamic contrast MR imaging of human prostate cancer xenograft tumors: a comparative study. Technol Cancer Res Treat. 2002;1:489–95.
- Kaighn ME, Narayan KS, Ohnuki Y, Lechner JF, Jones LW. Establishment and characterization of a human prostatic carcinoma cell line (PC-3). Invest Urol. 1979;17:16–23.
- Plonowski A, Nagy A, Schally AV, Sun B, Groot K, Halmos G. In vivo inhibition of PC-3 human androgen-independent prostate cancer by a targeted cytotoxic bombesin analogue, AN-215. Int J Cancer. 2000;88:652–7. CrossRef
- Shames DM, Kuwatsuru R, Vexler V, Muhler A, Brasch RC. Measurement of capillary permeability to macromolecules by dynamic magnetic resonance imaging: a quantitative noninvasive technique. Magn Reson Med. 1993;29:616–22. CrossRef
- Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis—correlation in invasive breast carcinoma. N Engl J Med. 1991;324:1–8.
- Kobayashi H, Reijnders K, English S, Yordanov AT, Milenic DE, Sowers AL, et al. Application of a macromolecular contrast agent for detection of alterations of tumor vessel permeability induced by radiation. Clin Cancer Res. 2004;10:7712–20. CrossRef
- Navone NM, Logothetis CJ, von Eschenbach AC, Troncoso P. Model systems of prostate cancer: uses and limitations. Cancer Metastasis Rev. 1999;17:361–71. CrossRef
- Tumor Characterization with Dynamic Contrast Enhanced Magnetic Resonance Imaging and Biodegradable Macromolecular Contrast Agents in Mice
Volume 26, Issue 9 , pp 2202-2208
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- biodegradable macromolecular contrast agent
- dynamic contrast enhanced MRI
- tumor characterization
- Industry Sectors
- Author Affiliations
- 1. Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah, USA
- 2. Department of Materials Science and Engineering, University of Utah, Salt Lake City, Utah, USA
- 3. Department of Radiology, University of Utah, Salt Lake City, Utah, USA
- 4. Department of Pathology, University of Utah, Salt Lake City, Utah, USA
- 5. Department of Biomedical Engineering, Case Western Reserve University, Wickenden 427, 10900 Euclid Avenue, Cleveland, Ohio, 44106-7207, USA