Positron emission tomography (PET) with (18)F-fluorodeoxyglucose ((18)F-FDG), a glucose analog, is widely used throughout the world as an indispensable imaging modality for the management of cancer treatment. This article reviews the pioneering achievements of PET in oncology with a focus on the development of PET that occurred from 1980 through the early-1990s. (18)F-FDG was first applied for imaging of animal tumors in 1980 and for brain tumor imaging clinically in 1982. (18)F-FDG enabled to visualize liver metastasis as clear positive image that could not be obtained by conventional nuclear imaging. Subsequently, (18)F-FDG was used for imaging various cancers, such as lung, pancreas, colorectal and hepatoma. (11)C-L-methionine ((11)C-MET) that reflects amino acid transport of cancers has an advantage that its uptake is lower in the brain and inflammatory tissue compared to (18)F-FDG, and was first applied for imaging lung cancer and brain tumor. (18)F-FDG and (11)C-MET were proved to be sensitive tracers that can be used to objectively evaluate the effectiveness of cancer treatment. The diagnostic accuracy of PET, which is critical in clinical practice, was evaluated for the differential diagnosis of malignant and benign lung nodules using (18)F-FDG or (11)C-MET. In addition to (18)F-FDG and (11)C-MET, many radiopharmaceuticals were developed, such as (18)F-labled thymidine analogs for evaluating proliferative activity, (18)F-fluoromisonidazole for imaging of hypoxia, and (18)F-fluorodeoxygalactose for evaluating liver-specific galactose metabolism and for imaging of hepatoma that retains galactose metabolic activity. These early efforts and achievements have greatly contributed to the development and clinical application of (18)F-FDG PET in oncology.

Intact antibodies are poor imaging agents due to a long serum half-life (10-20 d) preventing adequate contrast between the tumor and surrounding blood. Smaller engineered antibody fragments overcome this problem by exhibiting shorter serum half-lives (4-20 h).The diabody (55 kDa) is the smallest antibody fragment, which retains the bivalency of the intact antibody. Our goal was to develop and characterize the anti-CA19-9 diabody fragment and determine its ability to provide antigen specific imaging of pancreas cancer.

The diabody DNA construct was created by isolation of the variable region genes of the intact anti-CA19-9 antibody. Diabody expression was carried out in NS0 cells and purified using HPLC from supernatant. Specific antigen binding was confirmed with flow cytometry and immunofluorescence. Radiolabeled diabody was injected into mice harboring an antigen positive xenograft (BxPC3 or Capan-2) and a negative xenograft (MiaPaca-2). MicroCT and MicroPET were performed at successive time intervals after injection. Radioactivity was measured in blood and tumor to provide objective confirmation of the microPET images.

Immunofluorescence and flow cytometry showed specific binding of the anti-CA19-9 diabody. Pancreas xenograft imaging of BxPC3/MiaPaca-2 and Capan-2/MiaPaca-2 models with the anti-CA19-9 diabody demonstrated an average tumor:blood ratio of 5.0 and 2.0, respectively, and an average positive:negative tumor ratio of 11 and 6, respectively. With respect to the tumor:blood ratio, these data indicate five times and two times more radioactivity in the tumor than in the blood yielding adequate contrast between tumor tissue and background (i.e., blood) to create the representative microPET images.

We successfully engineered a functional diabody against CA19-9, a tumor antigen present on the vast majority of pancreas cancers. Additionally, we demonstrate high contrast antigen specific microPET imaging of pancreas cancer in xenograft models.

Several advances in genetics, diagnosis and palliation of pancreatic cancer (PC) have occurred in the last decades. A multidisciplinary approach to this disease is therefore recommended. PC is relatively common as it is the fourth leading cause of cancer related mortality. Most patients present with obstructive jaundice, epigastric or back pain, weight loss and anorexia. Despite improvements in diagnostic modalities, the majority of cases are still detected in advanced stages. The only curative treatment for PC remains surgical resection. No more than 20% of patients are candidates for surgery at the time of diagnosis and survival remains quite poor as adjuvant therapies are not very effective. A small percentage of patients with borderline non-resectable PC might benefit from neo-adjuvant chemoradiation therapy enabling them to undergo resection; however, randomized controlled studies are needed to prove the benefits of this strategy. Patients with unresectable PC benefit from palliative interventions such as biliary decompression and celiac plexus block. Further clinical trials to evaluate new chemo and radiation protocols as well as identification of genetic markers for PC are needed to improve the overall survival of patients affected by PC, as the current overall 5-year survival rate of patients affected by PC is still less than 5%. The aim of this article is to review the most recent high quality literature on this topic.

The preoperative evaluation of resectability for pancreatic cancer fails to identify up to 25% of patients who are unfortunately found to be unresectable at surgical exploration. Inoperative findings in this circumstance is usually due to either small volume metastatic disease or regional tumor invasion. While advances in computed tomography (CT) technology has increased accuracy of local tumor extent, occult metastatic disease remains a common problem. Although 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) has been demonstrated to be useful in the staging of many malignancies (e.g. esophageal cancer, recurrent colorectal cancer, lung cancer), it has not been found to significantly increase the accuracy of determining resectability preoperatively in pancreatic cancer, especially with regard to detection of small volume metastatic disease. There are a variety of pancreatic cancer-specific antigens which are being developed as a method for targeted molecular imaging; we provide preliminary data targeting the integrin alpha(v)beta(6) to demonstrate the potential feasibility of this approach. Further developments may allow the accurate determination of patients with resectable pancreatic cancer, and more importantly, those with unresectable disease that may forego unnecessary surgery, the associated morbidity, and the subsequent delay of appropriate therapy.

The purpose of this study was to estimate the usefulness of positron emission tomography (PET) in deciding on strategies for the treatment of pancreatic cancer. The following two parameters were evaluated: the ability of PET to provide an estimation of the progression of pancreatic cancer, and the ability of PET to predict survival and the effect of chemoradiotherapy.

Forty-two patients underwent PET as part of the procedure for making a diagnosis of pancreatic tumors. The maximum standardized uptake value (SUVmax) levels were compared with clinicopathological factors and analyzed.

PET provided a sensitivity of 87%, a specificity of 67%, and an overall accuracy of 85% for the diagnosis of pancreatic malignancy. Tumors with distant metastases showed significantly higher SUV levels than tumors without metastasis. In the patients who received chemoradiotherapy, the overall survival of the group in which SUVmax was less than 7.0 was better than that of the group in which SUVmax was more than 7.0.

We conclude that PET is a useful tool for determining pathological status and distant metastasis in pancreatic cancer, and for predicting the prognosis of patients receiving chemoradiotherapy.

Pancreatic carcinoma has a poor prognosis and early detection is essential for potentially curative resection. Despite the wide array of diagnostic tools, preoperative detection of small pancreatic carcinomas remains difficult. We report a case of small pancreatic carcinoma of the head of pancreas with indeterminate findings on US, ERCP, MRI and EUS which was successfully diagnosed via fusion CT-PET. This case illustrates the utility of CT-PET in the diagnosis of patients with small pancreatic carcinoma with equivocal findings on conventional diagnostic modalities.

The present review will provide an overview of the literature concerning the FDG PET diagnosis of pancreatic cancer and a summary from our experience of 231 cases of pancreatic lesions. FDG PET can effectively differentiate pancreatic cancer from benign lesion with high accuracy. Newly-developed PET scanners can detect small pancreatic cancers, up to 7 mm in diameter, by their high resolution, which could make a great contribution to the early detection of resectable and potentially curable pancreatic cancers. FDG PET is useful and cost-beneficial in the pre-operative staging of pancreatic cancer because an unexpected distant metastasis can be detected by whole-body PET in about 40% of the cases, which results in avoidance of unnecessary surgical procedures. FDG PET is also useful in evaluation of the treatment effect, monitoring after the operation and detection of recurrent pancreatic cancers. However, there are some drawbacks in PET diagnosis. A relatively wide overlap has been reported between semiquantitative uptake values obtained in cancers and those in inflammatory lesions. As for false-positive cases, active and chronic pancreatitis and autoimmune pancreatitis sometimes show high FDG accumulation and mimic pancreatic cancer with a shape of focal uptake. There were 8 false negative cases in the detection of pancreatic cancer by FDG PET, up to 33 mm in diameter, mainly because of their poor cellularity in cancer tissues. In addition, there are 19% of cancer cases with a decline in FDG uptake from 1 hr to 2 hr scan. FDG PET was recently applied to and was shown to be feasible in the differential diagnosis of cystic pancreatic lesions, such as intraductal papillary mucinous tumor of the pancreas. Further investigations are required to clarify the clinical value of FDG PET in predicting prognosis of the pancreatic patients.

To compare the diagnostic values of different methods for the differentiation of malignant from benign pancreatic lesions.

In 22 patients with focal pancreatic lesions, the carbohydrate antigen (CA) 19-9 level was measured; abdominal ultrasound (US), computed tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP), and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) were performed; and the value of these methods were analyzed for their use in cancer diagnosis.

Malignant lesions were identified in six patients and verified by surgery or clinical follow-up. The CA 19-9 level was elevated in four of the five patients examined (sensitivity, 80%). In all six cases, US and CT revealed hypoechogenic and hypodense areas (sensitivity, 100%). In one patient, ERCP was unsuccessful but yielded true-positive results in three others (sensitivity, 60%). The sensitivity of FDG PET was 100%. Sixteen focal cases of pancreatic disease proved to be benign. The CA 19-9 level was elevated in four of them (specificity, 73%). Hypoechogenic and hypodense areas were evident on US and CT in eight patients. The specificity of CT was 50% (8 of 16 cases). The specificity of US was 47% (7 of 15 cases). The specificity of successful ERCP was 92%. Fourteen negative FDG-PET results were truly negative. In two patients, however, the PET findings proved to be falsely positive (specificity, 88%).

FDG-PET is an effective tool to differentiate malignant from benign focal pancreatic lesions. In persons with focal pancreatic hypoechogenic or hypodense lesions detected by CT or US and an elevated CA 19-9 level, FDG PET should be the next step in the diagnostic strategy.

The purpose of this study was to investigate the feasibility of [18F]2-deoxy-2-fluoro-D-glucose (FDG) positron emission tomography (PET) in patients with a pancreatic mass by comparing the results with those of X-ray computed tomography (CT) and magnetic resonance (MR) imaging.

Eighty-six patients with pancreatic lesions, included 65 malignant tumors and 21 benign masses (55 masses were proven histologically and the others were diagnosed clinically), were studied. The diagnostic factors of CT and MR imaging were evaluated, and those of FDG PET were also evaluated for malignant and benign masses by visual interpretation and quantitative interpretation with the standardized uptake value (SUV) and SUVgluc which was designed to reduce the effects of a high blood sugar level. Visual interpretations were evaluated only in FDG PET images, and quantitative interpretations were evaluated by referring to CT and/or MR imaging. The correlation between SUV and the degree of histological differentiation in pancreatic ductal adenocarcinoma was investigated.

Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for CT imaging were 91, 62, 88, 68 and 84%, and for MR imaging 78, 70, 88, 54 and 76%, respectively. In visual interpretation of FDG PET images, the sensitivity, specificity, PPV, NPV and accuracy were 82, 81, 93, 59 and 81%, respectively. Significant differences between malignant and benign lesions existed in SUV and SUVgluc (p < 0.0001, each). With the cutoff value of SUV as 2.1 and SUVgluc as 2.2, the accuracy of diagnosis was maximal. With that cutoff value, the sensitivity, specificity, PPV, NPV and accuracy for SUV were 89, 76, 92, 70 and 86%, and for SUVgluc 91, 76, 92, 73 and 87%, respectively. The sensitivity and NPV of SUVgluc were higher than those of SUV, which suggests that SUVgluc may be more useful in reducing the number of overlooked malignant tumors. The specificity and PPV of FDG PET were superior to those of CT and MR imaging. There were no significant differences between the SUVs of moderately differentiated adenocarcinomas and those of well differentiated adenocarcinomas.

To improve the diagnostic procedure for classifying masses, FDG PET with not only SUV but also SUV corrected by the blood sugar level is required in addition to morphological diagnosis by CT and/or MR imaging.

The present review summarizes our strategies aimed at identifying and characterizing genetic alterations occurring at the transcriptional and chromosomal level in pancreatic cancer. To study transcriptional alterations we have used a number of techniques including modified versions of differential hybridizations and cDNA RDA (representational difference analysis). These approaches have led to the identification of more than 500 genes with differential expression in pancreatic cancer. To study chromosomal aberrations occurring in pancreatic cancer tissues we used comparative genomic hybridization (CGH). This allowed the identification of a number of chromosomal regions containing putative tumor suppressor genes or oncogenes. Genes isolated in both approaches represent potential new disease genes for pancreatic cancer and are at present being characterized by individual or serial analysis.

The clinical presentation of patients with pancreatic cancer may resemble the clinical picture of chronic pancreatitis. A definitive preoperative diagnosis is not always obtained in patients with a history of chronic pancreatitis despite the use of modern imaging techniques. Operative strategy therefore remains unclear before operation in these patients.

Positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) was introduced recently into clinical oncology because of its ability to demonstrate metabolic changes associated with various disease processes. The impact of FDG-PET on the differentiation of chronic pancreatitis and pancreatic cancer was investigated. FDG-PET was performed in 48 patients with chronic pancreatitis (n = 12), acute pancreatitis (n = 3) and pancreatic cancer (n = 27), and in controls (n = 6). Histological examination was undertaken in all cases except controls. The FDG-PET results were obtained without knowledge of results of other imaging procedures. The results were then compared with those of computed tomography, ultrasonography, endoscopic retrograde cholangiopancreaticography, operative findings and histology. PET images were analysed semiquantitatively by calculating a standard uptake value (SUV) 90-120 min after application of the tracer.

Cut-off values were validated as follows: SUV greater than 4.0 for pancreatic cancer, SUV of 3.0-4.0 for chronic pancreatitis, and SUV of less than 3.0 for controls. Sensitivity and specificity of PET imaging were 0.96 and 1.0 for pancreatic cancer, and 1.0 and 0.97 for chronic pancreatitis. In five cases only FDG-PET led to the correct preoperative diagnosis.

The results give further evidence that FDG-PET is an important non-invasive method for the differentiation of chronic pancreatitis and pancreatic cancer. Delayed image acquisition in the glycolysis plateau phase permits improved diagnostic performance. This imaging technique is extremely helpful before operation in patients with an otherwise unclear pancreatic mass, despite its costs.

Positron emission tomography (PET) is now primarily used in oncological indication owing to the successful application of fluorine-18 fluorodeoxyglucose (FDG) in an increasing number of clinical indications at different stages of diagnosis, and for staging and follow-up. This review first considers the biological characteristics of FDG and then discusses methodological considerations regarding its use. Clinical indications are considered, and the results achieved in respect of various organs and tumour types are reviewed in depth. The review concludes with a brief consideration of the ways in which clinical PET might be improved.

Positron emission tomography (PET) has become a very useful adjunct to anatomic imaging techniques, adding unique information to the characterization of disease. The whole-body PET FDG technique developed over the last few years has surpassed most expectations with respect to its utility in clinical oncology. The large spectrum of neoplasms that now can be studied with this approach makes it an essential clinical imaging tool in diagnosis and management for many patients with cancer. The metabolic information provided by this technique is complementary to results from standard clinical and morphological examinations. It may be anticipated that through application of the multi-modality imaging approach, significant advances in medical care will come.

The aim of this study was to examine the significance and problems of 2-[fluorine-18]-2-deoxy-d-glucose (FDG) positron emission tomography (PET) in diagnosing pancreatic cancer and mass-forming pancreatitis (MFP). PET, X-ray computed tomography (CT) and magnetic resonance (MR) imaging were performed in 15 patients with pancreatic cancer and nine patients with MFP. The areas of the PET scan were determined according to the markers drawn on the patients at CT or MR imaging. Regions of interests (ROIs) were placed by reference to the CT or MR images corresponding to the PET images. Tissue metabolism was evaluated by the differential absorption ratio (DAR) at 50 min after intravenous injection of FDG [DAR = tissue tracer concentration/(injected dose/body weight). The DAR value differed significantly in pancreatic cancer (mean +/- SD, 4.64 +/- 1.94) and MFP (mean +/- SD, 2.84 +/- 2.22) (P < 0.05). In one false-negative case (mucinous adenocarcinoma), the tumour contained a small number of malignant cells. In one false-positive case, lymphocytes accumulated densely in the mass in the pancreatic head. Further studies are necessary to investigate the histopathological characteristics (especially the cellularity) and other factors affecting the FDG DAR on PET images.