Will fledgling SPECT agent be the next FDG?

A new SPECT agent has the potential to launch the modern age of molecular imaging, according to its developer Cell Point. Philips Medical Systems believes strongly enough in the six-year-old Houston-based firm and its dream that it has groomed its SPECT/CT hardware and software to take advantage of this agent, called ECDG (ethylenedicysteine-deoxyglucose), when it reaches market, possibly as soon as mid-2008.

The two companies are betting that ECDG has what it takes to rival or even surpass FDG as the agent of choice when imaging certain types of cancer. But if ECDG is to truly challenge FDG as an all-around cancer imaging agent, its developer and partner can't go it alone. They will need the rest of the nuclear medicine industry onboard to smooth the way for widespread use of ECDG. The partners are already moving in that direction.

Because Philips and Cell Point wanted to demonstrate that the agent could be accurately imaged using a device other than one made by Philips, early clinical tests conducted at the University of Texas M. D. Anderson Cancer Center were done using Siemens imaging equipment. The researchers successfully transferred the raw data acquired with the Siemens system to a Philips workstation for postprocessing.

Since then, Philips and Cell Point have begun making plans to develop phantoms and reference data for use by any and all manufacturers of SPECT and SPECT/CT equipment to ensure that their devices can perform diagnostic scans with ECDG. Cell Point is well along in the development of easy-to-use "shake and shoot" kits to combine ECDG with technetium. Image resolution is down to 2 mm with results comparable to or better than those of FDG-PET images, based on side-by-side comparisons, according to Terry Colip, a Cell Point founder, now CFO and managing partner.

The company is also preparing to file an investigational new drug application with the FDA to begin testing a rhenium-188 tag on its ECDG carrier molecule.

"This will allow us to come full circle from diagnostic to therapeutic," Colip said.

The strategy is similar to one employed by the makers of Zevalin and Bexxar, each of which has passed FDA muster as a radioimmunotherapy agent against non-Hodgkin's lymphoma. The plan is for ECDG to follow in their footsteps, then leap well beyond.

ECDG will succeed partly because of its very small size, about 1/50 the size of the bulky monoclonal antibodies and MoAb fragments that up to now have ruled in molecular imaging and therapy. Sporting a molecular weight around 1000, it can slip through the cell wall of a cancer, first to visualize the cancer, then to irradiate it into oblivion.

"ECDG goes intracellular to destroy the tumor from the inside out," Colip said.

The agent is exceedingly flexible. ECDG is aggressively consumed by cancers with a high metabolic rate. This property opens the door to non-Hodgkin's lymphoma, as well as head and neck and lung cancers, but slams it shut for such low-metabolic-rate diseases as prostate cancer.

It also has a proclivity for the tissues responsible for ischemic heart disease. Preclinical studies have shown that when oxygen-starved tissues in the heart turn from metabolizing fatty acid to burning glucose, ECDG selectively accumulates in them.

This could pose a problem in the therapeutic stage of cancer treatment, as swapping gamma-emitting technetium for the beta-emitting rhenium would irradiate the ischemic myocardium as well as the cancer. Collateral damage would be limited by the 17-hour half-life of rhenium, however, and the higher metabolism of the cancer would predispose the agent toward greater accumulation in the tumor.

Clinical tests now under way are looking into the details of ECDG interaction with cells, primarily as an imaging agent. The tests are being spread across a half-dozen or so sites, including the University of Maryland and Johns Hopkins University, where a total of 100 to 120 cancer patients will undergo ECDG, as well as PET, scans in the months ahead.

If ECDG performs as Cell Point president Dr. F. David Rollo expects, the company could have an application in for FDA review by the end of this year. He's hoping for approval by mid-2008. Well in advance of that, Colip expects to have struck a partnership with an established radiopharmaceutical company to provide the infrastructure and distribution network to make ECDG a success.

Software for interpreting the images is already available for licensing through Cell Point and Philips (DI SCAN, 2/21/07, Philips, Cell Point hatch licensing plan for SPECT/CT component). And the hybrid systems for acquiring the data are on the market (DI SCAN, 2/20/07, Cell Point, Philips bet on next generation of radiotracers).

The result could achieve for SPECT what FDG has done for PET. Colip said he believes ECDG could be bigger than FDG. Rollo stops short of positioning the fledgling radiopharmaceutical as a replacement.

"We look at it as an imaging alternative for providers who don't have PET or don't have access to FDG," Rollo said. "They could have the confidence, using SPECT, to diagnose cancer, using biopsy to confirm."

On the therapy side, ECDG would be used to monitor treatment, as well as administer it - a hat trick that PET can never achieve.