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Use of PET can reduce, may eliminate more strenuous drug development trials with animals

A number of articles explore the use of positron emission tomography (PET) and small animal imaging--nonsurgical techniques that open the door to understanding and treating human diseases--in the April issue of the Society of Nuclear Medicine's Journal of Nuclear Medicine.

A major benefit of small animal imaging "is the ability to carry out many studies at various time points with the same animal," said SNM member Michael J. Welch, Ph.D., co-author of "Preparation, Biodistribution and Small Animal PET of 45Ti-Transferrin." Welch, a co-director of the division of radiological sciences at Washington University's renowned Mallinckrodt Institute of Radiology and head of the institute's radiochemistry laboratory, explained that studies on the same living animal can be extended over a period of time, allowing researchers to follow the development of disease in one subject and to monitor the effects of interventions on disease progression and outcome. Crucial information can be obtained noninvasively, repeatedly and quantitatively in the same animal, he said. With small animal imaging, one can very rapidly evaluate new radiopharmaceuticals using a limited number of animals and possibly eliminate the need for biopsies, extending an animal's life.

PET provides a noninvasive view into a person's living biology as it tracks a range of biological processes from metabolism to receptors, gene expression and drug activity. This imaging tool examines the chemistry and biology of a person's body by monitoring ingested tracer molecules, and it is used to study the metabolism of the brain, the heart and cancer. A miniature version of PET was developed and is used in much the same way to image small animals.

Small animals, especially mice, play a fundamental in the study of human biology and disease. Mice have nearly the same set of genes as humans, offering an opportunity to learn about the function of the many genes shared by both. This could lead to improved d iagnosis of disorders such as Alzheimer's and Parkinson's diseases, epilepsy, cardiovascular illnesses and many cancers. Researchers can gain a broader understanding of basic insights into normal physiology and disease processes to drug development and early response to anticancer and gene therapy. In addition, small animal imaging significantly reduces the preclinical evaluation time for therapeutic pharmaceuticals, possibly speeding the way for innovative drugs to patients, said Welch. Since there is no public registry of animal researchers, Welch estimates that there may be as many as 12,000 academic and private animal imaging labs in the world and that more than 200 may do small animal PET routinely.

Through small animal imaging research, Welch and his researchers gained more of an understanding about titanium anti-cancer drugs and new techniques for PET imaging with 45Ti, which they found to have excellent imaging characteristics and to be relatively inexpensive to produce. Welch and his researchers are also investigating the effect of cancer therapies on tumor function and performing cardiac studies that explore drugs that reverse the conditions of animals.

The JNM articles on small animal imaging, with numerous SNM members as authors, are listed here.

* Welch's co-author of "Preparation, Biodistribution and Small Animal PET of 45Ti-Transferrin" is Amy L. Vavere, Ph.D., Mallinckrodt Institute of Radiology at Washington University School of Medicine and the department of chemistry, Washington University, both in St. Louis, Mo.

* Authors of "Noninvasive Monitoring of Target Gene Expression by Imaging Reporter Gene Expression in Living Animals Using Improved Bicistronic Vectors" are Yanling Wang, Ph.D., and Meera Iyer, Ph.D., both with Crump Institute for Molecular Imaging and the department of molecular and medical pharmacology, David Geffen School of Medicine at UCLA, both in Los Angeles, Calif.; Alexander J. Annala, Ph.D ., Cedars-Sinai Medical Center, Los Angeles, Calif.; Steve Chappell, Ph.D., and Vincent Mauro, Ph.D., both with the department of neurobiology, Scripps Research Institute, Skaggs Institute for Chemical Biology, La Jolla, Calif.; and SNM member Sanjiv S. Gambhir, M.D., Ph.D., Crump Institute for Molecular Imaging and the department of molecular and medical pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, Calif., and the department of radiology, Bio-X Program, Stanford University School of Medicine, Stanford, Calif.

* "GRP Receptor-Targeted PET of a Rat Pancreas Carcinoma Xenograft in Nude Mice With a 68Ga-Labeled Bombesin(6?4) Analog" was written by Jochen Schuhmacher, Ph.D., department of diagnostic and therapeutic radiology, German Cancer Research Center, Heidelberg, Germany; Hanwen Zhang, M.S., Institute of Nuclear Medicine, University Hospital Basel, Basel, Switzerland; Josef Doll, Ph.D., department of diagnostic and therapeutic radiology, German Cancer Research Center, Heidelberg, Germany; Helmut R. Mäcke, Ph.D., Institute of Nuclear Medicine, University Hospital Basel, Basel, Switzerland; Ronald Matys, B.Sc., and Harald Hauser, B.Sc., both with the department of diagnostic and therapeutic radiology, German Cancer Research Center, Heidelberg, Germany; SNM members Marcus Henze, M.D., and Uwe Haberkorn, M.D., both with the department of nuclear medicine, University of Heidelberg, Heidelberg, Germany; and SNM member Michael Eisenhut, Ph.D., department of diagnostic and therapeutic radiology, German Cancer Research Center, Heidelberg, Germany.

* Authors of "Accuracy of Myocardial Sodium/Iodide Symporter Gene Expression Imaging With Radioiodide: Evaluation With a Dual-Gene Adenovirus Vector" are Kyung-Han Lee, M.D., Hye-Kyung Kim, B.S., and Jin-Young Paik, M.S., all with the department of nuclear medicine, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Korea; Takashi Matsui, M.D., Program in Card iovascular Gene Therapy, Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Mass.; Yearn Seong Choe, Ph.D., Yong Choi, Ph.D., and SNM member Byung-Tae Kim, M.D., all with the department of nuclear medicine, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Korea.

* "Biologic Correlates of Intratumoral Heterogeneity in 18F-FDG Distribution With Regional Expression of Glucose Transporters and Hexokinase-II in Experimental Tumor" was written by Songji Zhao, M.D., department of nuclear medicine and the department of tracer kinetics, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; SNM member Yuji Kuge, Ph.D., department of tracer kinetics, Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Takafumi Mochizuki, M.D., department of radiology, Nikko Memorial Hospital, Muroran, Japan; Toshiyuki Takahashi, M.D., department of pathology, Hokkaido Gastroenterology Hospital, Sapporo, Japan; SNM member Kunihiro Nakada, M.D., Masayuki Sato, B.S., Toshiki Takei, M.D., and SNM member Nagara Tamaki, M.D., all with the department of nuclear medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.


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Source:Society of Nuclear Medicine


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