World J. Surg. 20, 245–247, 1996

WORLD Journal of

SURGERY © 1996 by the Socie´te´ Internationale de Chirurgie

PET Scans of Abdominal Malignancy William H. Blahd, M.D.,1,2 Charles V. Brown, M.D.,1 Seyed A. Khonsary, M.D.,1 Judah B. Farahi, Ph.D.,1 Nayda Quinones, B.S.,1 Josephine Y. Ribe, B.S.,1 John J. Coyle Jr., M.D.,1,3 Edwin C. Glass, M.D.,1,3 Mark A. Mandelkern, Ph.D., M.D.1,3 1

Nuclear Medicine Service, West Los Angeles Veterans Affairs Medical Center, 11301 Wilshire Boulevard, Los Angeles, California 90073, U.S.A. Department of Medicine, UCLA School of Medicine, 10833 Le Conte Avenue, Los Angeles, California, 90095 U.S.A. 3 Department of Radiological Sciences, UCLA School of Medicine, 10833 Le Conte Avenue, Los Angeles, California, 90095 U.S.A. 2

Abstract. Positron emission tomography (PET) with fluorine-18-2-Ddeoxyglucose (FDG) currently is being integrated into clinical oncology because it provides unique functional information that can be applied to the management of cancer. In particular, it is useful for assessing tumor activity and growth, evaluating efficacy of therapy, and detecting tumor recurrence. Studies have demonstrated the value of whole-body PET-FDG imaging when staging and managing abdominal malignancy.

During the last decade there have been significant advances in imaging instrumentation. Computed tomography (CT) and magnetic resonance imaging (MRI) can now provide explicit detail of the structure of the human body and its maladies. The advent of positron emission tomography (PET) has made it possible to demonstrate chemical and metabolic changes associated with various disease processes. Investigations have shown that this technology may be applied to the measurement of functional alterations caused by cancer and may show promise for improving cancer detection and management.

Rationale The application of PET imaging to the study and detection of cancer is based on the early work of Warburg [1], who observed that malignant tissues had a high rate of aerobic and anaerobic glycolysis. This accelerated rate of tissue glycolysis has been related to increased activity of the glycolytic enzymes, hexokinase, phosphofructokinase, and pyruvate dehydrogenase. In addition, it has been observed that cancer cells exhibit accelerated glucose membrane transport. Some years later, Sokoloff and coworkers [2] demonstrated that the glucose analog 2-fluoro-2-deoxy-D-glucose, like glucose, is phosphorylated intracellularly by hexokinase; but unlike glucose, it is not metabolized further and remains trapped in the cell with a slow rate of dephosphorylation. After intravenous administration of 2-fluoro-2-deoxy-D-glucose labeled with positron-emitting fluorine 18 (FDG), it could be

Materials and Methods The PET scanner consists of a cylindrical array of thousands of scintillation crystal detectors that are interfaced with a powerful computer system. To perform a PET scan, a positron-emitting radioisotope tracer must be prepared by cyclotron bombardment. Chemical synthesis is required to incorporate the radioactive isotope into a radiopharmaceutical. The radioactive tracer is injected and the patient is then positioned within the PET scanner. The radioactive tracer molecules circulate throughout the body and are taken up by specific organ cells, such as brain cells. Emitted radiation is registered by the detector crystals within the PET scanner. Tomographic computer reconstruction of the distributed radiotracer is then undertaken to obtain the PET image. Correspondence to: W.H. Blahd, M.D.

Fig. 1. Comparative efficacy of PET and CT for detecting residual recurrent colorectal tumor (n 5 18). (Reprinted with permission of the publisher.)

246

Fig. 2. Whole-body PET image of patient with biopsy-proved cancer of the colon. The tumor (arrowhead) is visualized in coronal, transaxial, and sagittal projections. Normal FDG radioactivity concentration also is seen in the urinary bladder (heavy arrow) and myocardium (thin arrow) on the coronal view. Less intense background radioactivity is present in the kidneys and lungs.

demonstrated that the accumulation of FDG is proportional to cancer cell glycolytic activity. Glycolytic activity can be used to characterize a neoplasm as to its benignity or malignancy. It also has been shown that there is a relation between tumor glycolytic activity and the rate of tumor growth. Positron emission tomography provides unique in vivo information about tissue biochemistry and physiology. It often can detect abnormalities before structural changes have occurred. In vivo biochemical characterization is a method for classifying tumors and for planning and evaluating therapy. Furthermore, PET-FDG imaging may detect changes indicative of tumor response to therapy before alterations in structure occur. Studies have shown that essentially all human cancers accumulate FDG. Cancers routinely studied at most clinical PET centers include those of the brain, breast, colon and rectum, head and neck, liver, and lung, as well as lymphomas, melanomas, and musculoskeletal malignancies. The reported sensitivities, specificities, and accuracies of PET-FDG in these cancers are 80% or more [3]. The importance of PET-FDG in the study, diagnosis, and treatment of cancer, particularly when used in the whole-body imaging mode, is rapidly increasing. PET-FDG imaging can detect cancers that are suspected from clinical tests but are not found by other imaging techniques; and it can determine cancer spread in order to plan appropriate therapy. After treatment, it may be difficult to determine if cancer has recurred because the affected area may be scarred or distorted due to therapy. PET-FDG often can resolve this problem. Application of PET-FDG A typical application of PET-FDG is the workup of patients with colorectal cancer. Whole-body imaging is particularly valuable for

World J. Surg. Vol. 20, No. 2, February 1996

detecting and staging colorectal cancers. Gupta and Frick [4] have evaluated the preoperative staging of colorectal cancer using PET technology. They observed that the sensitivity, specificity, and predicted accuracy of PET-FDG was substantially better than that of CT (Fig. 1). In a small series of patients, they also observed higher sensitivity, specificity, and accuracy for PET-FDG than for CT for detecting recurrent tumor. They concluded that their findings indicate a clinically useful role for PET-FDG in the detection of recurrent or residual tumor following surgery or other therapy. Strauss et al. [5] studied 33 patients and were able to detect all recurrent tumor sites using standardized concentration values and tumor soft tissue ratios. Tumors were differentiated from scar tissue by quantitative evaluation of FDG uptake. Smith and coworkers [6] studied eight patients with liver metastases from adenocarcinoma of the colon or rectum. In all tumors, FDG was seen to accumulate in the rim around each tumor with a large central area showing no uptake. Ito et al. [7] compared the value of PET-FDG and MRI for differentiating recurrent rectal cancer and scar. In all 11 patients studied, increased FDG accumulation was observed in the tumor mass, whereas low FDG accumulation occurred in the presence of scar. MRI scans also could differentiate active tumor from scar in all but one case. These authors concluded that PET-FDG and MRI complement each other in the differential diagnosis of recurrent rectal cancer and scar. They stated further that PET-FDG may permit evaluation of the effect of therapy. Haberkorn and coworkers [8] studied 44 patients with recurrent colorectal carcinoma before and after radiotherapy. Plasma carcinoembryonic antigen (CEA) levels were measured immediately before PET-FDG studies. In 14 patients increased FDG uptake was associated with normal CEA values. In only two cases were normal FDG uptake values and increased CEA levels found, suggesting that PET-FDG is more sensitive than the measurement of CEA plasma levels for tumor recurrence. These authors have also observed that colorectal malignant lesions showed decreased FDG uptake after radiotherapy, suggesting the potential utility of PET-FDG for evaluating palliative therapy. There are few if any reports on the usefulness of PET-FDG imaging for detection of other abdominal malignancies. Goldberg and colleagues [9] studied 38 patients with known or suspected

Blahd et al.: PET and Abdominal Malignancy

malignancies involving the abdomen or pelvis that included, in addition to colon cancer, liver tumors and lymphoma. PET-FDG results were compared with CT results. Metastatic liver lesions often were more conspicuous on PET-FDG than CT, but two well differentiated primary liver lesions were not demonstrated by PET-FDG. The lesions in all but one patient with lymphoma were visualized. These authors pointed out the importance of clinical correlation, as inflammatory conditions may result in increased PET-FDG uptake. A typical PET-FDG study of a patient with colorectal cancer is seen in Figure 2. An intense concentration of FDG is observed at the tumor site. Note the normal concentration of FDG in the bladder, heart, and kidneys that must be differentiated from tumor uptake. Conclusions The future role of PET-FDG imaging will be influenced by the development of new and perhaps more effective tracers. PETFDG provides an opportunity to study the biochemical characteristics of tumors through the labeling of chemotherapeutic agents such as 5-fluorouracil [10]. In the near future it is likely that most imaging will be performed with FDG, however, which has already been shown to be a useful and effective tracer of cancer activity. FDG is an attractive agent in that its 2-hour half-life permits ready availability either in-house or from a nearby distribution center. It is expected that it will continue to be the imaging agent of choice for the next few years. Whole-body PET-FDG imaging is currently being rapidly integrated into clinical oncology because it provides unique functional information that can be applied to the management of cancer and, in particular, functional assessment of tumor activity and growth, evaluation of the efficacy of therapy, and detection of tumor recurrence. Re´sume´ La tomographie par ´emission de positons combine´e `a la fluorine18-2-D-de´soxy-glucose (TEP-FDG) trouve sa place actuellement en oncologie clinique car elle renseigne de manie`re unique sur les aspects fonctionnels du traitement du cancer. En particulier, elle est utile dans l’e´valuation de l’activite´ et la croissance tumorale,

247

l’e´valuation de l’efficacite ´ de the´rapie et la de ´tection des re ´cidives. Des ´etudes re ´centes ont de´montre ´ la valeur de la TEP-FDG dans le «staging» et le traitement des tumeurs malignes de l’abdomen. Resumen La tomografı´a por emisio ´n de positrones con fluor-18-2-D-desoxiglucosa (PET-FDG) esta´ siendo integrada a la oncologı´a clı´nica puesto que provee un tipo u ´nico de informacio ´n funcional que puede ser aplicada al manejo del ca´ncer. Es de particular utilidad en la evaluacio ´n de la actividad y del crecimiento tumorales, en la valoracio ´n de la eficacia de la terapia y en la deteccio ´n de recurrencia tumoral. Estudios recientes han demostrado el valor de la imagenologı´a corporal total con PET-FDG en la estadificacio ´n y el manejo de las neoplasias abdominales malignas. References 1. Warburg, O.: On the origin of cancer cells. Science 123:309, 1956 2. Sokoloff, L., Reivich, M., Kennedy, C.: The (14C) deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J. Neurochem. 28:897, 1977 3. Conti, P.S.: Positron emission tomography in clinical oncology. West. J. Med. 160:453, 1994 4. Gupta, N.C., Frick, M.P.: Clinical applications of positron-emission tomography in cancer. CA Cancer J. Clin. 43:235, 1993 5. Strauss, L.G., Clorius, J.H., Schlag, P., et al.: Recurrence of colorectal tumors: PET evaluation. Radiology 170:329, 1989 6. Smith, F.W., Heys, S.D., Evans, N.T., et al.: Pattern of 2-deoxy-2(18F)-fluro-D-glucose accumulation in liver tumours: primary, metastatic and after chemotherapy. Nucl. Med. Commun. 13:193, 1992 7. Ito, K., Kato, T., Tadokoro, M., et al.: Recurrent rectal cancer and scar: differentiation with PET and MR imaging. Radiology 182:549, 1992 8. Haberkorn, U., Strauss, L.G., Dimitrakopoulou, A., et al.: PET studies of fluorodeoxyglucose metabolism in patients with recurrent colorectal tumors receiving radiotherapy. J. Nucl. Med. 32:1485, 1991 9. Goldberg, M.A., Lee, M.J., Fischman, A.J., et al.: Fluorodeoxyglucose PET of abdominal and pelvic neoplasms: potential role in oncologic imaging. Radiographics 13:1047, 1993 10. Shani, J., Young, D., Schlesinger, T., et al.: Dosimetry and preliminary human studies of 18F-5-fluorouracil. Int. J. Nucl. Med. Biol. 9:25, 1982