Fenestra

Fenestra micro-CT Imaging Agents: Hepatocyte Selective, Long Residence Time in Blood and Completely Cleared

Fenestra® is a licensed technology that solves several key problems associated with micro-CT imaging. This biochemically activated emulsion is comprised of iodinated lipids that provide contrast enhancement and a novel oil-in-water lipid emulsion that selectively localizes the lipids for small animal imaging. The unique Fenestra® formulation is biodegradable and completely eliminated by hepatocyte metabolism. 

Here is a list (with clickable web links) of our Fenestra imaging Agents for In-Vivo imaging:

Fenestra® VC is a refined version of Fenestra® LC in which the surface of the lipid emulsion particles is modified so as to alter the recognition of the particle by the receptors on hepatocytes that are responsible for its uptake into the liver. With Fenestra VC, the delayed uptake by liver cells produces an agent with superior blood pool imaging properties that last for several hours after injection. Moreover, the agent remains truly intravascular so long as the endothelial integrity of the vessel is maintained. Like its liver-selective counterpart, Fenestra VC is eventually metabolized and eliminated through the hepatobiliary system.

Because of their comparatively long and stable in vivo residence times (up to several hours), the Fenestra® products have shown considerable promise for use in microCT imaging procedures. The numerous benefits provided by the Fenestra technology will play an instrumental role in facilitating the implementation of microCT imaging as an increasingly important and popular component of both basic research and commercial drug development.

Some examples of applications …

Fenestra LC Diabetes

Detection, staging and monitoring of mouse model of Diabetes with Fenestra LC

Video courtesy of Dr. Brian Ross, University of Michigan. Movie of bone and enhanced-blood isosurfaces in a mouse thoracic CT volume acquired with a Bruker Skyscan 1176 (~35um voxel size) with a 200 uL dose of MediLumine’s Fenestra VC injected in C57BL/6 female mouse.

Fenestra LC User Guide with MicroCAT II Imaging Hardware

Coronal view (left image) and 3D reconstruction (right image) of male Balb/c mouse with hepatic CT-26 adenocarcinoma 2 hr after IV injection of Fenestra LC. The CT-26 tumor is observed at the lower edge of the liver with a narrow rim of enhanced liver below the tumor and was colorized (purple) in the 3D reconstruction.

 

Publications

Oncology

  1. Lasnon C, Quak E, Briand M, Gu Z, Louis MH, Aide N. Contrast-enhanced small-animal PET/CT in cancer research: strong improvement of diagnostic accuracy without significant alteration of quantitative accuracy and NEMA NU 4-2008 image quality parameters. EJNMMI Res. 2013 Jan 17;3(1):5.
  2. Akladios CY, Bour G, Raykov Z, Mutter D, Marescaux J and Aprahamian M. Structural imaging of the pancreas in rat using micro-CT: application to a non-invasive longitudinal evaluation of pancreatic ductal carcinoma monitoring. J Cancer Res Ther. 2013, 1(2): 70–76
  3. Akladios CY, Bour G, Balboni G, Mutter D, Marescaux J, Aprahamian M. [Contribution of microCT structural imaging to preclinical evaluation of hepatocellular carcinoma chemotherapeutics on orthotopic graft in ACI rats]. Bull Cancer. 2011 Feb;98(2):120-32. doi: 10.1684/bdc.2011.1303.
  4. Martiniova L, Schimel D, Lai EW, Limpuangthip A, Kvetnansky R, Pacak K. In vivo micro-CT imaging of liver lesions in small animal models. Methods 50 (2010) 20–25
  5. Kitahashi T, Mutoh M, Tsurusaki M, Iinuma G, Suzuki M, Moriyama N, Yoshimoto M, Wakabayashi K, Sugimura T, Imai T. Imaging study of pancreatic ductal adenocarcinomas in Syrian hamsters using X-ray micro-computed tomography (CT). Cancer Sci. 2010 Jul;101(7):1761-6. Epub 2010 Apr 7.
  6. Rampurwala M, Ravoori MK, Wei W, Johnson VE, Vikram R, Kundra V. Visualization and quantification of intraperitoneal tumors by in vivo computed tomography using negative contrast enhancement strategy in a mouse model of ovarian cancer. Transl Oncol. 2009 May;2(2):96-106.
  7. Choukèr A, Lizak M, Schimel D, Helmberger T, Ward JM, Despres D, Kaufmann I, Bruns C, Löhe F, Ohta A, Sitkovsky MV, Klaunberg B, Thiel M. Comparison of Fenestra VC Contrast-enhanced computed tomography imaging with gadopentetate dimeglumine and ferucarbotran magnetic resonance imaging for the in vivo evaluation of murine liver damage after ischemia and reperfusion. Invest Radiol. 2008 Feb;43(2):77-91.
  8. Graham KC, Ford NL, MacKenzie LT, Postenka CO, Groom AC, MacDonald IC, Holdsworth DW, Drangova M, Chambers AF. Noninvasive quantification of tumor volume in preclinical liver metastasis models using contrast-enhanced x-ray computed tomography. Invest Radiol. 2008 Feb;43(2):92-9.
  9. Martiniova L, Ohta S, Guion P, Schimel D, Lai EW, Klaunberg B, Jagoda E, Pacak K. Anatomical and Functional Imaging of Tumors in Animal Models Focus on Pheochromocytoma. Ann. N.Y. Acad. Sci., 1073:392-404, 2006.
  10. Ohta S, Lai EW, Morris JC, Bakan DA, Klaunberg B, Cleary S, Powers JF, Tischler AS, Abu-Asab M, Schimel D, Pacak K. MicroCT for high-resolution imaging of ectopic pheochromocytoma tumors in the liver of nude mice. Int. J. Cancer, 119:2236-2241, 2006.
  11. Ohta S, Lai EQ, Taniguchi S, Tischler AS, Alesci S, Pacak K. Animal Models of Pheochromocytoma Including NIH Initial Experience. Ann. N.Y. Acad. Sci. 1073:300-305, 2006.
  12. Oldham M, Sakhalkar H, Oliver T, Wang YM, Kirpatrick J, Cao Y, Badea C, Johnson GA, Dewhirst M. Three-dimensional imaging of xenograft tumors using optical computed and emission tomography. Medical Physics. 33(9):2193-3202, 2006.
  13. Weber SM, Peterson KA, Durkee B, Qi C, Longino MA, Warner TM, Lee FT Jr, Weichert JP. Imaging of Murine Liver Tumor using MicroCT with a Hepatocyte-Selective Contrast Agent: Accuracy Is Dependent on Adequate Contrast Enhancement. J Surg Research, 119(1):41-5, 2004.
  14. Wisner ER, Weichert JP, Longino MA, Counsell RE. Percutaneous CT lymphography using a new polyiodinated biomimetic microemulsion. Academic Radiology 9:S191-93, 2002.
  15. Wisner ER, Weichert JP, Longino MA, Counsell RE, Weisbrode ST. A polyiodinated chylomicron remnant-like emulsion for percutaneous CT lymphography: synthesis and preliminary findings. Invest Radiol. 37(4):232-9, 2002.
  16. Weichert JP, Lee FT Jr., Chosy, SG, Longino MA, Kuhlman JE, Heisey DM, Leverson GE. Combined hepatocyte-selective and blood-pool contrast agents for the CT detection of experimental liver tumors in rabbits. Radiology 216:865-871, 2000.
  17. Weichert JP, Longino MA, Spigarelli MG, Lee Jr FT, Schwendner SW, Counsell RE. Computed Tomography Scanning of Morris Hepatoma with Liver-Specific Polyiodinated Triglycerides. Acad. Radiol. 3:412-417, 1996.
  18. Weichert JP, Lee FT Jr., Longino MA,Bakan DA, Spigarelli MG, Francis IR and Counsell RE. Computed tomography scanning of hepatic tumors with polyiodinated triglycerides. Acad. Radiol. Aug;3 Suppl 2:S229-31.

Angiogenesis and Vascular Anatomy

  1. Zhang Q, Du Y, Xue Z, Chi C, Jia X, Tian J. Comprehensive evaluation of the anti-angiogenic and anti-neoplastic effects of Endostar on liver cancer through optical molecular imaging. PLoS One. 2014 Jan 8;9(1):e85559.
  2. Zagorchev L1, Oses P, Zhuang ZW, Moodie K, Mulligan-Kehoe MJ, Simons M, Couffinhal T. Micro computed tomography for vascular exploration. J Angiogenes Res. 2010 Mar 5;2:7.
  3. Lopez-Soler RI, Brennan MP, Goyal A, Wang Y, Fong P, Tellides G, Sinusas A, Dardik A, Breuer C. Development of a Mouse Model for Evaluation of Small Diameter Vascular Grafts. J Surgical Research, 139(1):1-6, 2007.
  4. Price JR, Aykac D, Wall J. “Improvements in Level Set Segmentation of 3D Small Animal Imagery” in Medical Imaging 2007: Image Processing. Ed. Pluim JP and Reinhardt JM. Proceedings of the SPIE, Volume 6512, p 651233, 2007.
  5. Gary CK, Park H, Lombardo LW, Piestrup MA, Cremer JT, Pantell RH, Dudchik YI. High Resolution X-ray Microscope. Applied Physics Letters, 90:181111-1-181111-3. 2007.
  6. Goyal A, Wang Y, Su H, Dobrucki LW, Brennan M, Fong P, Dardik A, Tellides G, Sinusas A, Pober JS. Development of a model system for preliminary evaluation of tissue-engineered vascular conduits. J Pediatric Surgery. 41:787-791. 2006.
  7. Badea CT, Hedlund LW, De Lin M, Boslego Mackel JF, Johnson GA. Tumor imaging in small animals with a combined micro-CT/micro-DSA system using iodinated conventional and blood pool contrast agents. Media Mol Imaging. 2006 Jul-Aug;1(4):153-64.
  8. Avenell, J. Evaluating non-invasive microPET/CT imaging of K-562 myelosarcoma for monitoring tumor growth and angiogenesis in untreated and treated mice. J Nucl Med. 2006; 47 (Supplement 1):556P
  9. Tobin KW, Aykac D, Govindasamy VP, Gleason SS, Gregor J, Karnowski TP, Price JR, Wall J. “Image-Based Informatics for Preclinical Biomedical Research” in Lecture Notes in Computer Science, Volume 4292:1740-1750. 2006. G. Bebis et.al. (Eds): ISCV 2006.
  10. Langheinrich AC and Ritman EL. Quantitative Imaging of Microvascular Permeability in a Rat Model of Lipopolysaccharide Induced Sepsis: Evaluation Using Cryostatic Microcomputed Tomography. Investigative Radiology. 41(8):645-650, 2006.
  11. Li XF, Zanzonico P, Ling CC, O’Donoghue J. Visualization of experimental lung and bone metastases in live nude mice by X-ray micro-computed tomography. Technol Cancer Res Treat. 2006 Apr;5(2):147-55.
  12. Kindlmann GL, Weinstein DM, Jones GM, Johnson CR, Capecchi MR, Keller C. Practical vessel imaging by computed tomography in live transgenic mouse models for human tumors. Mol Imaging. 2005 Oct-Dec;4(4):417-24.

Cardiovascular Disease Research

  1. Vandeghinste B, Trachet B, Renard M, Casteleyn C, Staelens S, Loeys B, Segers P, Vandenberghe S. Replacing vascular corrosion casting by in vivo micro-CT imaging for building 3D cardiovascular models in mice. Mol Imaging Biol. 2011 Feb;13(1):78-86.
  2. Sheikh AY, van der Bogt KE, Doyle TC, Sheikh MK, Ransohoff KJ, Ali ZA, Palmer OP, Robbins RC, Fischbein MP, Wu JC. Micro-CT for characterization of murine CV disease models. JACC Cardiovasc Imaging. 2010 Jul;3(7):783-5.
  3. Dinkel J, Bartling SH, Kuntz J, Grasruck M, Kopp-Schneider A, Iwasaki M, Dimmeler S, Gupta R, Semmler W, Kauczor HU, Kiessling F. Intrinsic gating for small-animal computed tomography: a robust ECG-less paradigm for deriving cardiac phase information and functional imaging. Circ Cardiovasc Imaging. 2008 Nov;1(3):235-43.
  4. Detombe SA, Ford NL, Xiang F, Lu X, Feng Q, Drangova M. Longitudinal follow-up of cardiac structure and functional changes in an infarct mouse model using retrospectively gated micro-computed tomography. Invest Radiol. 2008 Jul;43(7):520-9.
  5. Drangova M, Ford NL, Detombe SA, Wheatley AR, Holdsworth DW. Fast retrospectively gated quantitative four-dimensional (4D) cardiac micro computed tomography imaging of free-breathing mice. Invest Radiol. 2007 Feb;42(2):85-94.
  6. Badea CT, Hedlund LW, Mackel JF, Mao L, Rockman HA, Johnson GA. Cardiac micro-computed tomography for morphological and functional phenotyping of muscle LIM protein null mice. Mol Imaging. 2007 Jul-Aug;6(4):261-8.
  7. Nahrendorf M, Badea C, Hedlund LW, Figueiredo J-L, Sosnovik DE, Johnson GA, Weissleder R. High Resolution Imaging of Murine Myocardial Infarction With Delayed Enhancement Cine Micro-CT. Am J Physiol Heart Circ Physiol, 292(6): H3172-8, 2007.
  8. Ford NL, Graham KC, Groom AC, MacDonald IC, Chamber AF, Holdsworth DW. Time-Course Characterization of the Computed Tomography Contrast Enhancement of an Iodinated Blood-Pool Contrast Agent in Mice Using a Volumetric Flat-Panel Equipped Computed Tomography Scanner. Investigative Radiology. 41(4):384-390, 2006.
  9. Badea CT, Bucholz E, Hedlund LW, Rockman HA, Johnson GA. Imaging Methods for Morphological and Functional Phenotyping of the Rodent Heart. Toxicologic Pathology. 34:111-117, 2006.
  10. Badea CT, Fubara B, Hedlund LW, Johnson GA. 4D Micro-CT of the Mouse Heart. Molecular Imaging. 4(2): 110-116, 2005.

Multimodal Imaging (Cancer, Diseases)

  1. Lasnon C, Quak E, Briand M, Gu Z, Louis MH, Aide N. Contrast-enhanced small-animal PET/CT in cancer research: strong improvement of diagnostic accuracy without significant alteration of quantitative accuracy and NEMA NU 4-2008 image quality parameters. EJNMMI Res. 2013 Jan 17;3(1):5.
  2. Wall JS, Kennel SJ, Richey T, Allen A, Stuckey A, Weiss DT, Macy SD, Barbour R, Seubert P, Solomon A, Schenk D. Generation and characterization of anti-AA amyloid-specific monoclonal antibodies. Front Immunol. 2011 Aug 8;2:32.
  3. Gabie de Jong, Thijs Hendriks, Rob Bleichrodt, Martin Gotthardt, Eric Visser, Wim Oyen and Otto Boerman. FDG-PET, CT and MRI for the detection of experimental colorectal liver metastases: An exploratory study. J Nucl Med. 2011; 52 (Supplement 1):312
  4. Tsui B, Mok G, Wang Y, Taso A, Bedja D, Yu J, Gabrielson K, Nimmagadda S, Bengal F, Pomper M. High-resolution small animal SPECT/CT imaging of atherosclerotic plaques in ApoE-/- mice using Tc-99m Annexin-V and contrast enhanced CT. J Nucl Med. 2007; 48 (Supplement 2):103P
  5. Tsui B, Mok G, Wang Y, Taso A, Bedja D, Yu J, Gabrielson K, Nimmagadda S, Bengal F, Pomper M. High-resolution small animal SPECT/CT imaging of atherosclerotic plaques in ApoE-/- mice using Tc-99m Annexin-V and contrast enhanced CT. J Nucl. Med. 48(S2):103P, 2007.
  6. Wall JS, Kennel SJ, Paulus M, Gregor J, Richey T, Avenell J, Yap J, Townsend D, Weiss DT, Solomon A. Radioimaging of light chain amyloid with a fibril-reactive monoclonal antibody. J Nucl Med. 2006 Dec;47(12):2016-24.
  7. Avenell, J. Evaluating non-invasive microPET/CT imaging of K-562 myelosarcoma for monitoring tumor growth and angiogenesis in untreated and treated mice. J Nucl Med. 2006; 47 (Supplement 1):556P
  8. Isobe s, Tsimikas S, Zhou J, Fujimoto S, Sarai M, Branks MJ, Fujimoto A, Hofstra L, Reutelingsperger CP, Murohara T, Virmani R, Kolodgie FD, Narula N, Petrov A, Narula J. Noninvasive Imaging of Atherosclerotic Lesions in Apolipoprotein E-Deficient and Low-Density-Lipoprotein Receptor –Deficient Mice with Annexin A5. J Nucl Medicine. 2006 47:1497-1505.
  9. Wall JS, Kennel SJ, Paulus MJ, Gleason S, Gregor J, Baba J, Schell M, Tichey T, O’nuallain B, Donnell R, Hawkins PN, Weiss DR, Solomon A. Quantiitative high-resolution microradiographic imaging of amyloid deposits in a novel murine model of AA amyloidosis. Amyloid: The Journal of Protein Folding Disorders. 12(3):149-156, 2005.
  10. Aykac D, Price JR, Wall JS. 3D Segmentation of the Mouse Spleen in microCT via Active Contours. 2005 IEEE Nuclear Sciences Symposium Conference Record. M03-91, p1542-1545.
  11. Weichert JP, Perlman SB, Lee FT, Johnson CD, Coyle TM, Bennet L. Comparison of a hepatocyte-selective polyiodinated triglyceride CT contrast agent and FDG-PET in the woodchuck model of spontaneous hepatocellular carcinoma. Radiologic Society of North America, 87th Annual Meeting, Chicago IL, 2001.