Volumetric computed tomography (VCT): a new technology for noninvasive, high-resolution monitoring of tumor angiogenesis

Volumetric computed tomography (VCT) is a technology in which area detectors are used for imaging large volumes of a subject with isotropic imaging resolution. We are experimenting with a prototype VCT scanner that uses flat-panel X-ray detectors and is designed for high-resolution three-dimensional (3D) imaging. Using this technique, we have demonstrated microangiography of xeno-transplanted skin squamous cell carcinomas in nude mice. VCT shows the vessel architecture of tumors and animals with greater detail and plasticity than has previously been achieved, and is superior to contrast-enhanced magnetic resonance (MR) angiography. VCT and MR images correlate well for larger tumor vessels, which are tracked from their origin on 3D reconstructions of VCT images. When compared with histology, small tumor vessels with a diameter as small as 50 μm were clearly visualized. Furthermore, imaging small vessel networks inside the tumor tissue improved discrimination of vital and necrotic regions. Thus, VCT substantially improves imaging of vascularization in tumors and offers a promising tool for preclinical studies of tumor angiogenesis and antiangiogenic therapies.

[1]  M. Bahner,et al.  Regional blood flow, capillary permeability, and compartmental volumes: measurement with dynamic CT--initial experience. , 1999, Radiology.

[2]  M. Vannier,et al.  Spiral (helical) CT. , 1993, Radiology.

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

[4]  M. Brechbiel,et al.  Micro‐MR angiography of normal and intratumoral vessels in mice using dedicated intravascular MR contrast agents with high generation of polyamidoamine dendrimer core: Reference to pharmacokinetic properties of dendrimer‐based MR contrast agents , 2001, Journal of magnetic resonance imaging : JMRI.

[5]  L. Schad,et al.  Dynamic T1‐weighted monitoring of vascularization in human carcinoma heterotransplants by magnetic resonance imaging , 2003, International journal of cancer.

[6]  R. Kerbel.  Tumor angiogenesis: past, present and the near future. , 2000, Carcinogenesis.

[7]  S. Fox,et al.  Angiogenesis: pathological, prognostic, and growth-factor pathways and their link to trial design and anticancer drugs. , 2001, The Lancet. Oncology.

[8]  P. Carmeliet,et al.  Angiogenesis in cancer and other diseases , 2000, Nature.

[9]  Michael D Feldman,et al.  Tumor vessel development and maturation impose limits on the effectiveness of anti-vascular therapy. , 2003, The American journal of pathology.

[10]  C. Corot,et al.  CT pulmonary angiography with a macromolecular contrast medium: a comparative study versus iobitridol in rabbits. , 2001, Investigative radiology.

[11]  J. Folkman,et al.  Angiogenesis-dependent diseases. , 2001, Seminars in oncology.

[12]  C. Rinker-Schaeffer,et al.  Differentiation of nonmetastatic and metastatic rodent prostate tumors with high spectral and spatial resolution MRI , 2001, Magnetic resonance in medicine.

[13]  N. Fusenig,et al.  Multiple stages and genetic alterations in immortalization, malignant transformation, and tumor progression of human skin keratinocytes , 1998, Molecular carcinogenesis.

[14]  K. Miles,et al.  Standardized perfusion value: universal CT contrast enhancement scale that correlates with FDG PET in lung nodules. , 2001, Radiology.

[15]  F. Scappaticci.  Mechanisms and future directions for angiogenesis-based cancer therapies. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  Mihaela Skobe,et al.  Halting angiogenesis suppresses carcinoma cell invasion , 1997, Nature Medicine.

[17]  J. Folkman,et al.  The role of angiogenesis in tumor growth. , 1992, Seminars in cancer biology.

[18]  Rakesh K. Jain,et al.  Normalizing tumor vasculature with anti-angiogenic therapy: A new paradigm for combination therapy , 2001, Nature Medicine.

[19]  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.

[20]  Leo P Lawler,et al.  Three-dimensional CT angiography with multidetector CT data: study optimization, protocol design, and clinical applications in the abdomen. , 2002, Critical reviews in computed tomography.

[21]  J. Folkman.  Angiogenesis in cancer, vascular, rheumatoid and other disease , 1995, Nature Medicine.

[22]  M Kono,et al.  Solitary pulmonary nodules: evaluation of blood flow patterns with dynamic CT. , 1997, Radiology.

[23]  Rakesh K Jain,et al.  Molecular regulation of vessel maturation , 2003, Nature Medicine.

[24]  M. Port,et al.  Preclinical Profile of the Monodisperse Iodinated Macromolecular Blood Pool Agent P743 , 2001, Investigative radiology.

[25]  G. Yancopoulos,et al.  Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. , 1999, Science.

[26]  M. Bock,et al.  High‐resolution three‐dimensional MR angiography of rodent tumors: Morphologic characterization of intratumoral vasculature , 2003, Journal of magnetic resonance imaging : JMRI.

[27]  Nobunao Maehara,et al.  Experimental microcomputed tomography study of the 3D microangioarchitecture of tumors , 2003, European Radiology.