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Multimodal system contributes to advances in stem cell therapy

Jul 2007
Gary Boas

Stem cell therapy can benefit patients suffering from a variety of serious conditions, including myocardial infarction leading to heart failure. Studies in a recent issue of The New England Journal of Medicine outlined the benefits of using autologous (the patient’s own) bone marrow-derived stem cells for cardiac treatment. The research also showed, however, that only 2 to 5 percent of administered stem cells will reach and remain in the heart, limiting the overall success of the therapy.

CellCyte Genetics Corp. of Kirkland, Wash., is working to discover and develop stem cell therapeutic products — modified versions of naturally occurring proteins — that will make delivery of the cells to specific organs much more specific and efficient. The company initially is focusing on products for patients with myocardial infarction. In early studies with these drugs, 70 to 80 percent of cells reached the heart, and a large portion of them remained there.

The drugs were discovered using a single-photon-emission computed tomography (SPECT) system. To aid in their development, the company recently purchased the NanoSpect/CT system from Bioscan Inc. of Washington. The high-resolution system combines SPECT with conventional x-ray CT. SPECT alone provides an intensity signal from an injected probe, often giving researchers only a fair idea of the area from which the signal originated, especially in the case of novel probes. “To get really precise localization, you need an anatomic map of the animal,” said H. Andreas Kalmes, CellCyte’s vice president of pharmacology. Conventional CT offers a “very nice picture of the skeleton” and even some degree of soft tissue contrast. The combined system offers coregistration of the SPECT and CT signals and thus provides the localization of the former that the company needs.


An animal-imaging system combining SPECT and x-ray CT offers coregistration of intensity signals and anatomic maps, enabling precise localization of the signals in an animal. A company is planning to use the system to develop stem cell therapeutic products, initially for patients with myocardial infarction.

The challenge to developing the system was improving the resolution for use in animals while maintaining sensitivity. In humans, organs are imaged with resolutions just under 1 cm. Organs in a mouse, however, are roughly 1500 times smaller than those in a human. Therefore, submillimeter resolution is needed to achieve the same relative resolution. “Submillimeter resolution was possible before,” said Jack Hoppin of Bioscan, “though not really in a reasonable amount of time; namely, not with adequate sensitivity.” Through advances in both hardware and software, the system can provide submillimeter resolution with sufficient sensitivity.

It employs up to four gamma cameras, each equipped with multipinhole apertures, affording the SPECT submillimeter resolution. The large area and intrinsic resolution of the camera combined with multipinhole apertures enable the acquisition of high-resolution images without excessive scan times. Coregistration of SPECT and CT is possible because instrumentation for the two modalities is mounted on the same helical scanning mechanism. Image acquisition is performed by continuously stepping the animal through the field of view along the same axis of rotation as the camera’s.

The instrumentation for the SPECT and CT systems is mounted on the same helical scanning mechanism, enabling precise coregistration of the two modalities. Each of the gamma cameras is equipped with multipinhole apertures, allowing submillimeter resolution with SPECT.

Kalmes noted that the system was chosen from among only three commercially available SPECT/CT systems dedicated to small-animal imaging. CellCyte and Bioscan have signed an agreement to collaborate to develop the system further for the specific needs of a drug-developing company. Representatives from the two companies will meet regularly, primarily to discuss ways in which to optimize the software for dual-isotope imaging. “We will be able to track the localization of the delivered stem cells and at the same time monitor the biodistribution of our drugs, which is very important for us,” Kalmes said. They also intend to streamline data tracking, to keep track of all of the study parameters so they are readily available when the time comes to submit an application to the FDA.

CellCyte will install the SPECT/CT system in its new corporate headquarters and large-scale research facilities in Bothell, Wash., which it will occupy in September. It plans to use the system for studies designed to complete the investigational new drug application process, in this case for following delivery of the stem cells to the heart. “If we don’t give our drug or if we give a control, then the majority of the cells will go to the spleen and liver,” Kalmes said. “With our drug, most will go to the heart.”

The SPECT/CT system will enable the company to demonstrate the efficacy of the drug in organ-specific cell delivery. It plans to submit an investigational new drug application later this year for the first human safety trials. In addition, it will launch similar studies for other products in the pipeline.

Contact: H. Andreas Kalmes, CellCyte Genetics Corp.; e-mail:; Jack Hoppin, Bioscan Inc.; e-mail: jhop

Basic ScienceBiophotonicsResearch & Technologysingle-photon-emission computed tomography (SPECT) systemstem cell therapy

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