By: Hadas Goshen and Prof. Ora Israel Director of the Nuclear Medicine Institute, Rambam Health Care Campus, Dr. Rachel Bar-Shalom Director of the PET-CT unit, Nuclear Medicine Institute, Rambam Health Care Campus, Dr. Zohar Keidar Deputy Director of the Nuclear Medicine Institute, Rambam Health Care Campus
One of the major and most important battlefields in the war against cancer is focused on accurate disease diagnosis and determination of the extent to which the disease has spread. Accurate evaluation of the status of the disease may save lives and enable the physicians to adjust the appropriate treatment, which may defeat the disease in its early stages, while it is still limited and only localized to a certain area. At this stage, it is still possible to cure the disease, for example by resection of the lesion, before it begins to send its destructive branches (metastases) spreading to other parts of the body. Furthermore, accurate diagnosis of disseminated disease may prevent the suffering and complications associated with unnecessary surgery, for patients in whom the disease has already metastasized. It is also important for physicians to have an objective tool for evaluation of the response to treatment and for follow-up aimed at detecting disease recurrence or new metastatic lesions.
The accepted diagnostic approach is based on several imaging techniques for evaluating diseases such as cancer, with each modality providing a different aspect of the disease. The treating physician who receives this data attempts to combine and compose the cumulative information into a complete picture of the disease. Hybrid imaging technology was introduced in 1999, so we are celebrating a decade of its clinical use this year! This technology enables performance of two sequential imaging tests in the same patient using a single imaging device during a single imaging session. These two sequential imaging modalities provide complementary information regarding the status of a specific disease process.
SPECT-CT and PET-CT are imaging methods combining anatomical imaging (CT) with functional/metabolic imaging obtained by means of nuclear medicine procedures. Although developed and introduced into clinical practice simultaneously, PET-CT was the first device to gain wide clinical acceptance, mainly for cancer diagnosis, with SPECT CT now being used with increasing frequency for evaluation of cancer and other diseases, such as infections and coronary artery diseases. The widespread use of hybrid imaging in a variety of clinical indications is based on the information that has been accumulated from scientific studies, many of which have been performed by the Nuclear Medicine Institute at Rambam, a pioneer in demonstrating the incremental value of this new non-invasive diagnostic test.
The PET-CT technology combines two devices: one is an X-ray imaging device (the well known CT), which rotates around the patient and provides information that is processed by a computer into a detailed 2D image of the anatomical structures along multiple cross sections of the body.
The second modality is a PET device that creates tomographic images of positron emitting radioactive materials. This is a metabolic imaging method, which demonstrates live tissue activity.
Each of the modalities has known limitations. The image provided by CT reveals anatomical details, which, however, are sometimes difficult to define in terms of clinical significance, because they lack information on the function and type of tissue in the specific anatomic structure. "Since a CT image defines a disease according to enlargement of organs and changes in tissue density, lymph nodes that are affected by the disease but not yet enlarged will not be identified by CT," explains Dr. Rachel Bar-Shalom, director of the PET-CT unit of the Nuclear Medicine Institute at Rambam Medical Center. "On the other hand, lymph nodes can be enlarged due to a non-malignant process such as inflammation, and they may be falsely interpreted as a malignant tumor according to the CT
."
An additional limitation of the CT is the fact that it is sometimes difficult to determine the precise location of the suspicious finding in the presence of treatment-related anatomic distortion. In 1999-2000, engineers at the General Electric Healthcare R&D plant in Israel developed the first prototype of their PET-CT system. The system underwent accelerated development, with researchers in the Nuclear Medicine Institute at Rambam, led by Prof. Israel, playing a pioneering role in defining medical applications and diagnostic criteria for the combined imaging modality.
"We were the first to realize the medical value of the combined device. The contribution of the combination of the two technologies exceeds the sum of the contribution of each of the two components" emphasizes Prof. Ora Israel, Director of the Nuclear Medicine Institute, and a world expert in the field of combined imaging, "The whole is bigger than the sum of its parts."
PET-CT: all the answers in a single test
The conventional diagnostic approach includes performance of each imaging test separately, and it is difficult to compare the results obtained by the various imaging tests. For example, there may be errors in identifying the precise location of the malignant lesion, due to variations in the patient's position between the different tests, or variations in the location or even the volume of the various organs of the body, etc.
Using the hybrid technology, all the data is collected during a single non-invasive test at a high precision level. In addition to the accuracy of the diagnosis, this procedure spares the patient from additional prolonged examinations and the stressful period of waiting for the results until the diagnosis is received.
The image obtained can provide answers to many clinical questions:
• Whether the lesion is malignant or benign - as reflected in the activity level. A malignant tumor consumes much more glucose, compared with a benign tumor or a malignant tumor that has been suppressed or cured by radiotherapy or chemotherapy (which, however, may still appear as a suspicious mass in a CT scan).
• Location of the tumor: can be obtained with high precision from the combined image, thus providing important topographic landmarks guiding further invasive tests: the biopsy needle, for example, can be targeted directly towards the location of a suspicious focus of enhanced radiotracer uptake, thus enabling precise diagnosis and assisting the surgeon in reaching the tumor intended for resection.
• Are metastases present?
• Is there recurrent disease?
• Therapy planning: Identification of the tumor foci helps oncologists to determine the most appropriate treatment (resection, radiotherapy, chemotherapy or combined treatment), and assists in accurate planning of the optimal treatment.
• Monitoring treatment efficacy
• Improvement of the physician's confidence in the accuracy of the diagnosis
Only the tip of the iceberg…
At present, the most frequent application of PET-CT is in the field of oncology. The new system is used for initial disease staging, monitoring of the response to treatment and detection of distal metastases or signs of disease recurrence in cancer patients.
"According to our estimates, in one out of four cases the diagnostic and the therapeutic approaches are changed following PET-CT imaging," indicates Prof. Israel.
"About 40,000 PET-CT tests have been performed at Rambam since 2001, a unique number, compared with global experience. In numerous studies performed by us since the initial breakthrough a decade ago, which involved development of tools for scientific evaluation of this imaging method in cancer patients, we discovered a variety of medical applications for different cancer types, different time points throughout the period of treatment and monitoring of the disease," says Dr. Bar-Shalom, and she specifies diseases including lymphomas (lymph node cancer), esophageal cancer, lung cancer, breast cancer, cervical cancer, colon cancer and various types of head and neck cancer.
PET-CT is also used for diagnosis in cases of elevated blood levels of tumor markers, without any assisting evidence for the potential presence of disease provided by other imaging techniques.
The magic bullet
What about combination of other imaging techniques? Dr. Zohar Keidar, Deputy Director of the Nuclear Medicine Institute at Rambam, indicates that the hybrid technology that is currently under development, but not yet routinely applied, is the PET-MRI. This is a device that combines functional isotope imaging (PET) with MRI examination, and SPECT-US, a nuclear camera combined with an ultrasound device.
According to Dr. Keidar, one of the "hot" fields of PET-CT application in oncology is a software connection of the diagnostic device to therapeutic devices, with the ability to deliver focused radiotherapy with a high degree of precision. Dr. Keidar summarizes the possibilities inherent in the combined technologies: "The sky is the limit!"
According to Dr. Bar-Shalom, the need for and importance of combined imaging will increase in the future, with the main research fields involving a continuous search for new and more specific tracers, probes that will only mark the diseased tissues, and not other targets. For example, radioactive glucose is absorbed by malignant tissue, but also by benign tumors and healthy tissue. The trend is to develop radioactive materials that will enable specific imaging of specific diseases by a "magic bullet". The implementation of these specific radiotracers demands a combination of specific information on the functional status of the disease and accurate anatomic information, providing a "road map" to the location of the sites of disease in the body, enabling a more accurate diagnosis, and influencing the subsequent care given to the patient.
Currently, PET-CT is included in the Israeli Basket of Health for the diagnosis, staging and monitoring of cancer, for the location of an epileptic focus in the brain prior to surgery, and for cardiac testing prior to making a decision about a heart transplant, based on the determination of viability of the damaged myocardium.
The potential of the device is now being examined for additional clinical applications in cardiology, infectious diseases, endocrinology and neurology.
"We are still only scraping the tip of the iceberg," promises Prof. Israel, "and I'm sure that additional surprises are waiting around the corner."