Department of Radiology

Small Animal Imaging (SPECT/CT) Laboratory

 

Resources for Small Animal Imaging

(Small Animal Imaging Resources at the Children’s Cancer Research Center can be found at http://ccri.uthscsa.edu/ImagingFacility.html )

 

The small animal imaging resources in the Department of Radiology are dedicated to the performance of cutting edge research that uses imaging for directing the development of new therapeutic agents. The use of imaging devices especially manufactured for small animal imaging has improved the quality and understanding of information derived from each research study while greatly decreasing the number of animals required for a particular research project. Many images can be acquired at different time points in the same animal and the ability to study the effect of therapeutic interventions longitudinally in the same animal can greatly improved the statistical comparisons of therapeutic effect. Investigators in this department have specific skills and experience in small animal anesthesia and other advanced techniques such as molecular ligand synthesis and radiolabeling of biological molecules and nanoparticles. These resources are available for interdepartmental collaborations as well as collaborations with investigators off-campus. The Radiology Department has specific focuses of research in molecular imaging and nanotechnology, diabetes, interventional oncology, radiofrequency ablation and vascular biology (stent) research.

 

Small Animal Imaging Devices

Multimodality imaging: microCT/SPECT by Gamma Medica for mouse, rat and rabbit models of disease.

 

micro CT/SPECT

 

 

 

micro CT/SPECT

 

 

 

 

 

 

 

CT/SPECT mouse image 1A representative set of SPECT-CT mouse images administered with Ag2/PRA cDNA-transfected DCs labeled with In-oxime. The scintigraphic images are superimposed on CT images to enable anatomical marking of the radioactivity disposition. Awasthi: et al Journal of Immunology, Sept. 15, 2005.

 

 

 

 

 

CT/SPECT mouse image 2 Bone metastasis lumbar spine Volume Rendered micro CTImage

 

 

 

 

 

 

 

 

 

microCT/SPECT specifications:

  • Two gamma cameras decreases imaging time and increases time resolution 80 Kev CT camera
  • Capable of rapid CT/SPECT image fusion.
  • Rapid 3D volume reconstruction and image superimposition.
  • Tracking of traditional nuclear medicine compounds with 99mTc.
  • Can use all clinically available single photon radionuclides such as 99mTc- heart perfusion agents, 99mTc-renal imaging agents, 111In-WBCs.

Multimodality Micro CT/PET for imaging of mouse, rat and rabbit models of human disease processes will be added soon.

 

Whole Body CT image Whole Body FDG-PET image Fused PET/CT image
Whole Body CT
Whole Body FDG-PET
Fused PET/CT

 

  • Hi-resolution PET camera mounted on existing Gamma Medica frame
  • Precise anatomic co-registration of anatomical CT images and physiologic PET images.
  • F-18 FDG fluorodeoxyglucose (2 hour half-life) available from RIC and/or local commercial suppliers

 

 

Volune Rendered FDG-PET
Volume Rendered CT Bone Window
Fused Volume Rendered PET/CT

Volume Rendered

FDG-PET

Volume Rendered

CT Bone Window

Fused Volume

Rendered PET/CT

 

Pictures are courtesy of Gamma Medica-Ideas. If you would like to visit their site please go to: http://www.gammamedica.com/fleximages.php

 

 

 

• Cu-64 (12 hour half-life) for labeling antibodies and bacteria available from Washington University.

 

CT/SPECT mouse image 3 Distribution of 64Cu-labeled tularemia bacteria in mice following intranasal administration

 

 

 

 

 

 

 

 

 

• Contact person for research using the microCT/SPECT/PET is Dr. Beth Goins, 210 567-5535

 

 

• Standard clinical Picker Nuclear Medicine SPECT camera for use in larger animals such as rabbits and baboons.

 

PET image 99mTc-labeled standard and long circulating liposomes in rabbits

 

 

 

 

 

 

 

 

 

 

• Whole mouse optical imaging system housed and maintained in the optical imaging facility.

 

 

PET image 2Picture is Courtesy of Dr. Kay Oyajobi, UTHSCSA, Cellular & Structural Biology

 

 

 

 

 

 

 

 

 

 

 

• Access to full complement of clinical imaging devices (CT, MRI, MRS, US, etc. at UHS and or VA).

 

 

Small Animal Imaging Consultation and Support

• Dedicated image analysis software, computers and consultants

• Contact person for research using the Image Analysis Facility is Dr. Geoffrey Clarke, 210-567-5550.

Imaging pharmaceutical laboratory with radiopharmacist, radiochemist, organic chemist, and molecular biologist to develop new labeling methods

• Contact person for research using the Imaging Pharmaceuticals is Dr. James Wang, 210-567-0672.

Preparation of models for imaging studies (small animal handling, model development, anesthesia, and imaging procedures.

• Contact person for research using Imaging Model Preparation is Dr. Vibhu Awasthi, 210-567-5542.


Extensive small animal imaging technical assistance through imaging physics faculty and graduate student assistants.

• Contact person for research using Imaging Physics is Dr. Gary Fullerton, 210-567-5550.

 

 

Radiology Personnel Supporting Small Animal Research:

Dr. Phillips, MD - Nuclear Medicine physician with extensive small animal imaging experimental design and imaging expertise.

 

Dr. Goins, PhD- Lipid biochemist with extensive small animal imaging expertise. Expertise in liposome manufacture and encapsulation of drugs. Extensive experience in small animal experimental design and imaging as well as development of animal models of infection and tumor. Development of novel methods of radiolabeling liposomes. Expertise with microSPECT/CT imaging.

 

Dr. Awasthi, PhD- Pharmaceutical formulation expert also a radiopharmacist with extensive small animal imaging and surgical expertise. Extensive small animal expertise in microPET oxygen-15 imaging and SPECT small animal imaging. Labeling of proteins with SPECT imaging agents.

 

Dr. Wang, PhD- radiochemist with much microPET small imaging experience and biologic background. Expertise in design of imaging ligands and development of novel drug delivery agents.

 

Dr. Bao, PhD- dual appointment with the Radiology department and the ENT department. PhD Graduate of Radiological Sciences Radiochemist and medical physicist working on head and neck cancer projects and Radiology projects for treatment of solid tumors. Specific expertise in radiotherapeutic nuclides, small animal cancer models and small animal imaging.

 

Dr. Gao, PhD- organic chemist with extensive experience in ligand development

 

Dr. Han, PhD- molecular biologist with expertise in siRNA and aptamer technology

 

Dr. Clarke, PhD- MRI physicist with animal MRI expertise and extensive medical background and knowledge. Extensive experience with MRI cardiac imaging in animals. Expertise in image analysis in animal models.

 

Dr. Peng, PhD- recently recruited MRI physicist. Will be working on collaboration with Philips Corporation in human and animal imaging.

 

Dr. Sprague, PhD- vascular biologist, extensive experience in rabbit and pig angiographic studies. These studies are currently being performed in the Experimental Surgical Suite of LAR of veterinarian. Jim Elliot Chun Ruan will be receiving PhD soon and joining our department as post-doctoral fellow. Dr. Ruan has extensive experience in image analysis in human and small animals.

 

Dr. Gary Fullerton, PhD- medical physicist and director of the radiological sciences graduate program with extensive experience in imaging methodologies, especially MRI.

 

 

Small Animal Imaging Expertise in the Department of Radiology

 

Personnel in the Radiology have worked in small animal imaging for the past twenty years but recently added personnel to encompass an even wide range of necessary expertise necessary to promote NIH fundable animal imaging based research. The list available expertise includes:

  • Small animal anesthesia in mice, rats and rabbits
  • Imaging of mice, rats and rabbits with microSPECT/CT
  • Imaging of rats and rabbits with standard planar gamma camera and SPECT
  • Small Animal surgery for catheterization of rat femoral artery and vein for drug administration and blood sampling
  • Head and neck and breast rat tumor models
  • Autoimmune colitis rat model
  • Localized infection models in thigh and bone
  • Imaging of mice bone tumor models including myeloma and breast cancer bone mets
  • Development of models for lymph node drug delivery including rabbit leg, rat peritoneal and rat pleural space.
  • Imaging analysis and statistical comparison of image data in small animals.
  • Imaging of baboons with SPECT
  • 3D reconstruction project with Dr. Schenken
  • Drug Delivery
  • Nanotechnology
  • Liposome formulation and radiolabeling with 99mTc, 111In and 186Re and 188Re
  • Liposome hemoglobin and drug encapsulation
  • Interest and some experience in imaging other nanotechnology
  • Radiopharmacy and pharmaceutical formulation expertise
  • Radiochemistry expertise
  • Organic chemistry expertise
  • Molecular biology expertise
  • MRI expertise
  • Radiofrequency ablation and other local cancer therapy expertise

 

 

 

Small Animal Publications from the Department of Radiology

Publications from the Radiology Department have included an extensive list of project dependent on small animal imaging including the following topics:

  • Rabbits and indium-labeled platelets for studying distribution of platelets on stents.
  • Work was done on the original Palmaz stent.1-3
  • Method related to a new improved method for labeling liposomes with 99mTc as studied in rabbits.4, 5
  • 99mTc-liposomes for infection targeting in rats.6, 7

PET image 3

 

 

99mTc-liposome for imaging and drug delivery to thigh abscess in rat.9

 

 

 

 

 

 

  • 99mTc-liposomes for inflammation targeting.8

 

PET image 4
Accumulation of 99mTc-liposome in colitis
  • Blood substitute distribution studies in rats and rabbits.5, 10, 11
  • Studies with radiolabeled platelets in rats. 9, 12, 13
  • Distribution of 99mTc-labeled insulin in rats. 14
  • Lymph node drug targeting to popliteal nodes in rabbits.15

 

PET image 5

 

  • Intraperitoneal and intrapleural lymph node targeting in rats.16-18
  • Oxygen-15 delivery by blood substitute in rats.18-20

 

PET image 6 PET image 7
Baseline oxygen-15 in rat
Post 40% hemorrhagic shock in rat

 

  • Long circulating liposomes in rabbits10, 11, 21-24
  • Rhenium labeling of liposomes for tumor therapy in rats.25, 26
  • Imaging of commercially available Doxil (doxorubicin-liposomes) in rats.26
  • Bone marrow targeted 99mTc-liposomes

PET image 8

 

  • T-cell imaging using microPET in mice 27, 28
  • Gastric emptying study in Zucker diabetic rats.29
  • Cardiac MRI imaging in dogs.30

 

References

1. Miller DD, Boulet AJ, Tio FO, et al. In vivo technetium-99m S12 antibody imaging of platelet alpha-granules in rabbit endothelial neointimal proliferation after angioplasty. Circulation. Jan 1991;83(1):224-236.

2. Miller DD, Rivera FJ, Garcia OJ, Palmaz JC, Berger HJ, Weisman HF. Imaging of vascular injury with 99mTc-labeled monoclonal antiplatelet antibody S12. Preliminary experience in human percutaneous transluminal angioplasty. Circulation. Apr 1992;85(4):1354-1363.

3. Palmaz JC, Windeler SA, Garcia F, Tio FO, Sibbitt RR, Reuter SR. Atherosclerotic rabbit aortas: expandable intraluminal grafting. Radiology. Sep 1986;160(3):723-726.

4. Phillips WT, Rudolph AS, Goins B, Timmons JH, Klipper R, R B. A simple method for producing a technetium-99m-labeled liposome which is stable in vivo. Nucl Med Biol. 1992;19:539-547.

5. Rudolph AS, Klipper RW, Goins B, Phillips WT. In vivo biodistribution of a radiolabeled blood substitute: 99mTc-labeled liposome encapsulated hemoglobin in an anesthetized rabbit. Proc Natl Acad Sci USA. 1991;88:10976-10980.

6. Goins B, Klipper R, Rudolph AS, Cliff RO, Blumhardt R, WT P. Biodistribution and imaging studies of technetium-99m labeled liposomes in rats with focal infection. J Nucl Med. 1993;34:2160-2168.

7. Awasthi VD, Goins B, Klipper R, Loredo R, Korvick D, Phillips WT. Comparison of dual radiolabeled liposomes (DRL), Tc-99m-MDP and Ga-67 citrate for imaging osteomyelitis in rabbit model. J. Nucl. Med. 1997;38:182P.

8. Awasthi V, Goins B, McManus L, Klipper R, Phillipsa WT. [99mTc] liposomes for localizing experimental colitis in a rabbit model. Nucl Med Biol. Feb 2003;30(2):159-168.

9. Goins B, Aggarwal SK, Klipper R, et al. Technetium-99m-labeled liposomes versus gallium-67 citrate for detection of hyperoxia-induced lung inflammation in rats. J. Nucl. Med. 1997;38:185P.

10. Awasthi VD, Garcia D, Klipper R, Goins BA, Phillips WT. Neutral and anionic liposome-encapsulated hemoglobin: effect of postinserted poly(ethylene glycol)-distearoylphosphatidylethanolamine on distribution and circulation kinetics. J Pharmacol Exp Ther. Apr 2004;309(1):241-248.

11. Awasthi VD, Garcia D, Klipper R, Phillips WT, Goins BA. Kinetics of liposome-encapsulated hemoglobin after 25% hypovolemic exchange transfusion. Int J Pharm. Sep 28 2004;283(1-2):53-62.

12. Goins B, Phillips WT, Klipper R, Rudolph AS. Role of complement in rats injected with liposome-encapsulated hemoglobin. J Surg Res. Mar 1997;68(2):99-105.

13. Phillips WT, Klipper R, Fresne D, Rudolph AS, Javors M, Goins B. Platelet reactivity with liposome-encapsulated hemoglobin in the rat. Exp Hematol. Dec 1997;25(13):1347-1356.

14. Awasthi V, Gambhir S, Sewatkar AB. 99mTc-insulin: labeling, biodistribution and scintiimaging in animals. Nucl Med Biol. Feb 1994;21(2):251-254.

15. Phillips WT, Klipper R, Goins B. Novel method of greatly enhanced delivery of liposomes to lymph nodes. J Pharmacol Exp Ther. Oct 2000;295(1):309-313.

16. Medina LA, Calixto SM, Klipper R, Phillips WT, Goins B. Avidin/biotin-liposome system injected in the pleural space for drug delivery to mediastinal lymph nodes. J Pharm Sci. Oct 2004;93(10):2595-2608.

17. Medina LA, Klipper R, Phillips WT, Goins B. Pharmacokinetics and biodistribution of [111In]-avidin and [99mTc]-biotin-liposomes injected in the pleural space for the targeting of mediastinal nodes. Nucl Med Biol. Jan 2004;31(1):41-51.

18. Phillips WT, Lemon L, Goins B, et al. The use of 15O-O2 to measure oxygen carrying capacity of blood substitutes in vivo. American Journal of Physiology. 1997;(in press).

19. Phillips W, Goins B. Targeted delivery of imaging agents by liposomes. In: Torchilin VP, ed. Handbook of Targeted Delivery of Imaging Agents. Boca Raton: CRC Press; 1995:149-173.

20. Phillips WT, Lemen LD, Goins B, et al. Oxygen carrying capacity and tissue oxygen delivery of liposome encapsulated hemoglobin using oxygen-15-labeled molecular oxygen. Artificial Cells, Blood Substitutes and Immobilization Biotechnology. 1996;24:403.

21. Awasthi V, Meinken G, Springer K, Srivastava SC, Freimuth P. Biodistribution of radioiodinated adenovirus fiber protein knob domain after intravenous injection in mice. J Virol. Jun 2004;78(12):6431-6438.

22. Awasthi VD, Garcia D, Goins BA, Phillips WT. Circulation and biodistribution profiles of long-circulating PEG-liposomes of various sizes in rabbits. Int J Pharm. Mar 6 2003;253(1-2):121-132.

23. Phillips WT, Klipper RW, Awasthi VD, et al. Polyethylene glycol-modified liposome-encapsulated hemoglobin: a long circulating red cell substitute. J Pharmacol Exp Ther. Feb 1999;288(2):665-670.

24. Sou K, Klipper R, Goins B, Tsuchida E, Phillips WT. Circulation kinetics and organ distribution of Hb-vesicles developed as a red blood cell substitute. J Pharmacol Exp Ther. Feb 2005;312(2):702-709.

25. Bao A, Goins B, Klipper R, Negrete G, Phillips WT. 186Re-liposome labeling using 186Re-SNS/S complexes: in vitro stability, imaging, and biodistribution in rats. J Nucl Med. Dec 2003;44(12):1992-1999.

26. Bao A, Goins B, Klipper R, Negrete G, Phillips WT. Direct 99mTc labeling of pegylated liposomal doxorubicin (Doxil) for pharmacokinetic and non-invasive imaging studies. J Pharmacol Exp Ther. Feb 2004;308(2):419-425.

27. Matsui K, Wang Z, McCarthy TJ, Allen PM, Reichert DE. Quantitation and visualization of tumor-specific T cells in the secondary lymphoid organs during and after tumor elimination by PET. Nucl Med Biol. Nov 2004;31(8):1021-1031.

28. Wipke BT, Wang Z, Kim J, McCarthy TJ, Allen PM. Dynamic visualization of a joint-specific autoimmune response through positron emission tomography. Nat Immunol. Apr 2002;3(4):366-372.

29. Green GM, Guan D, Schwartz JG, Phillips WT. Accelerated gastric emptying of glucose in Zucker type 2 diabetic rats: role in postprandial hyperglycaemia. Diabetologia. Feb 1997;40(2):136-142.

30. Clarke GD, Eckels R, Chaney C, et al. Measurement of absolute epicardial coronary artery flow and flow reserve with breath-hold cine phase-contrast magnetic resonance imaging. Circulation. May 15 1995;91(10):2627-2634.