A recent television mystery show I was watching had many people searching for a suspect without success — that is, until the authorities brought in a bloodhound to “sniff” out the suspect. The dog took them on an entirely new path and, of course, they found the suspect!
This story is a metaphor for our search for cancer. We send out a lot of people to search for a tumor: radiologists, nuclear medicine specialists, cytologists, gastroenterologists, pathologists, ultrasonographers, and other physicians and health care professionals — and they search blindly, hoping to find a tumor early enough to make a difference.
Even after the diagnosis, this Keystone Kops’ activity continues periodically or with each new symptom. And the physician and patient are never really sure if they are missing something too small to detect with existing technology. Is there still tumor out there metastatic to some distant place, slowly growing?
On the treatment front, pharmaceutical companies have developed targeted therapies that, to use another metaphor, hone-in on a receptor like a heat-seeking missile. But similar technology has yet to be created to actually help find the tumor.
To be fair, there have been new radiopharmaceuticals developed that are more sensitive to specific diseases, but if we could muse a bit, would it not be an interesting development to use a target technology approach as a radiological tool that would cause the resulting image to glow in the dark?
Well, this idea is not mine and it has gone well beyond the muse stage. It is the idea of small, privately held company, NuView Life Sciences, located in Park City, Utah. Working in conjunction with several university medical centers across the country, they are on the cusp of an exciting new technology for imaging.
Their concept is to couple the rapidly expanding knowledge of molecular biology with the developments in imaging technology. They are doing this by taking a biomarker that is fused with a radioactive nuclide of copper (Copper 64). As Copper 64 decays, it emits a positron that can be detected by a positron emission tomography (PET) scanner.
To understand this technology, here is how a PET scanner works. Currently, about 90 percent of all PET scans use radioactive glucose as the imaging compound. The glucose is made to be radioactive by adding an atom of radioactive fluorine, which upon decaying emits the positron. The new molecule is called 2-fluorodeoxy-D-glucose (FDG). Once infused into the patient, FDG acts almost like regular glucose and is taken up by cells that are rapidly metabolizing glucose.
But, the cells cannot fully metabolize FDG and as a result, radioactive fluorine accumulates in the cells. So, in principle, those cells that are most actively metabolizing glucose “light up” as the radioactive decay occurs and the positron is emitted. Of note is that as this molecule decays it shoots out specific particles at around 180 degrees from each other. This action allows the camera to “plot” where the emission is occurring and can be processed into a three-dimensional image.
But this is only half of the picture. The PET scan results are increasingly being co-registered with either a CT or MRI scan, allowing an overlay of the different images.The combination incorporates structure (CT and MRI) with function (PET) capabilities producing amazing potential for seeing exactly where the metabolically-active tumor is located.
But this new technology is not relying on glucose as the primary substrate as glucose is not as specific to tumors as we would like it to be.
NuView has chosen other biomarkers to seek out specific receptors that are in some way related to a specific type of tumor cell. For instance, for melanoma NuView has developed a radioactive tagged alpha-melanocyte-stimulating-hormone (MSH). This peptide binds specifically to melanocortin-1 receptors that are over-expressed on malignant melanoma cells. As this tagged alpha MSH binds to the receptor, it “lights up” the tumor cells like no other previous technology!
For prostate cancer, NuView has chosen to tag a compound called VPAC1. This is a receptor that is over expressed on prostate cancer cells and can be targeted with a special gene that is guided by a radioactive probe.
It is thought that this radiopharmaceutical imaging molecule will detect prostate cancer earlier than a urologist‘s finger or an elevated prostate specific antigen (PSA) level.
NuView is also working on a molecular imaging agent that targets sites of inflammation, infection, and non-Hodgkin’s lymphoma using a small molecule that is specific to white cells.
None of these products are available yet. In fact, many have only been studied in animal models. The company has limited experience in patients. But the proof of concept has been done and it is only a matter of time until the investigational new drug applications are filed.
The biggest problem with the new technology is the difficulty and expense of creating the radioactive particles. This requires a cyclotron. Few institutions have access to this technology and because of the very short half life of the actual radioactive particle, the facility must be relatively close to the hospital that is conducting the PET scan.
In addition, many of these particles degrade over just a few hours. Thus, they cannot be shipped across the country.
Medical imaging is one of the fastest growing sectors of the health care budget. It is creating huge challenges for insurers and payers attempting to control costs, and for good reasons. Let’s face it, humans are visual creatures. We love seeing things, like photographs, Facebook, weather maps, and tumor sites! And seeing leads to understanding and treating. Physicians have been searching for better imaging since Wilhelm Röntgen took the first X-ray of his wife’s hand on Dec. 22, 1895.
The number of imaging modalities has skyrocketed in the past quarter century. Despite the promise, the development of these new imaging radiopharmaceuticals will only make the management more challenging. But, they will give hope to millions of people facing an uncertain future. These imaging compounds are a picture of Tomorrow’s Medicine!