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PURPOSE: Positron emission tomography (PET) is an imaging technique based on in vivo cellular metabolism. Increased glucose metabolism in neoplastic cells is detected by using fluorine-18 deoxyglucose. In an ongoing pilot study to determine the usefulness of this technique, PET is compared with computerized tomography (CT) for the preoperative staging of colorectal carcinoma. METHODS: Sixteen patients were evaluated with both PET and CT of the abdomen and pelvis. Results were compared with operative and histopathologic findings. Fifteen malignant lesions were found in 16 patients by histology. PET had a positive predictive value of 93 percent and a negative predictive value of 50 percent. By comparison CT had a positive predictive value of 100 percent and a negative predictive value of 27 percent. CONCLUSIONS: These preliminary results indicate that PET has increased sensitivity for staging colorectal carcinoma, whereas CT has higher specificity. The predictive value of a positive PET compares favorably with CT. Furthermore, the predictive accuracy for detection of colorectal carcinoma is 83 percent for PET and 56 percent for CT.

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No-carrier-added (NCA) (+-)-p-[18F]fluoroamphetamine (2a) and (+-)-6-[18F]fluoro-3,4-methylene-dioxy-amphetamine (2b) were synthesized through a multistep synthesis by nucleophilic substitution of the appropriate precursors (p-nitrobenzaldehyde, 1a and 6-nitropiperonal 1b, respectively) with [18F]fluoride followed by condensation with nitroethane and reduction with LAH in 20-30% yield (EOB) in a synthesis time of 90-109 min from EOB. NCA (-)-[11C]methamphetamine (4a) and (+-)-3,4-methylene-dioxy-N-[11C]methamphetamine (4b) were synthesized by methylation of the appropriate desmethyl precursors 3a and 3b with [11C]H3I in 40-60% yield (EOB) in a synthesis time of 30 min from EOB. Animal studies in mouse and rat revealed that the relative tissue uptake of these radiotracers was kidneys > lungs > liver > spleen > brain > heart > blood. The uptakes of these radiotracers in mouse brain were high and similar at 5 min post-injection (approx. 5%/g) but radioactivity then declined rapidly (approx. 1%/g at 60 min post-injection). For compounds 2a and 2b, the activity in the femur did not increase with time indicating in vivo defluorination may not be the major route of metabolism. Monoamine uptake inhibitors (nomifensine, fluoxetine and nisoxetine) did not inhibit but enhance the uptake of (-)-[11C]methamphetamine (4a) in the rat brain by greater than 50%. A PET study in a Rhesus monkey revealed that the uptakes of (-)-[11C]methamphetamine in different brain regions were similar and the retention of the radioactivity in these regions remained constant throughout the study. Analysis of arterial plasma by HPLC showed that 50% of radioactivity remained as 4a at 60 min post-injection.

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BACKGROUND: Positron emission tomography (PET), a new noninvasive imaging modality, utilizing 2-[F-18]-fluoro-2-deoxy-D-glucose (FDG), has demonstrated increased FDG uptake in lung tumors. OBJECTIVE: To determine the diagnostic efficacy of PET-FDG imaging in differentiating benign from malignant solitary pulmonary nodules. PATIENT SELECTION: A prospective study of 30 patients who presented with indeterminate solitary pulmonary nodules less than 3 cm in size based on chest radiograph and computed tomographic (CT) scan. SETTING: Two tertiary care medical centers in Omaha, Neb: Creighton University Medical Center and the Omaha Veterans Administration Medical Center. MEASUREMENTS: Positron emission tomographic imaging of the lung was performed 1 h after intravenous injection of 10 mCi of F-18-FDG. Qualitative analysis of the images was performed independently by two observers by visual identification of the areas of increased FDG uptake in the lung nodules. Semiquantitative analysis was performed using computation of differential uptake ratio (DUR). Histologic specimens were obtained in 29 patients (thoracotomy 20, transthoracic needle aspiration biopsy 8, bronchoscopy 1). RESULTS: Positron emission tomographic imaging correctly identified 27 of 30 pulmonary nodules. Diagnostic accuracy was high with sensitivity of 95 percent and specificity of 80 percent. The positive and negative predictive value of PET imaging for solitary pulmonary nodules was 90 percent and 89 percent, respectively. The DUR values were significantly higher for malignant nodules (mean +/- SD, 5.55 +/- 2.79) than benign nodules (mean +/- SD, 0.95 +/- 0.99) (p < 0.001). There was one false-negative result in a patient with a 1-cm nodule identified as a scar adenocarcinoma. There were two false-positive cases and both had caseating granulomas with active inflammation and Histoplasma organisms. CONCLUSION: PET-FDG imaging of the lung, a new noninvasive diagnostic test, has a high degree of accuracy in differentiating benign from malignant pulmonary nodules. PET-FDG imaging could complement CT scanning in the evaluation and treatment of patients with solitary pulmonary nodules.

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A potential antipsychotic drug, BMY 14802 was labeled with 18F and its distribution in rodents was studied. No-carrier-added (NCA) (+/-)-[18F]BMY 14802 (5) was synthesized by two methods in 5-10% radiochemical yield in a synthesis time of 130-140 min from EOB with a specific activity of 0.5-1.5 Ci/microM. (+)- and (-)-[18F]BMY 14802 was synthesized by the chiral reduction of alpha-(4-[18F]fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine-b utanone (4) with chiral reducing agent, (+)- and (-)-beta-chlorodiisopinocampheylborane [(+)- and (-)-DIP chloride] in 6-10% radiochemical yield in a synthesis time of 150 min from EOB. Animal studies in mouse and in rat revealed that the distribution of 5 in each tissue was high at 5 min, the radioactivity then declined rapidly in all tissues studied except in the liver and in the small intestine. The radioactivity in the femur did not increase with time indicating in vivo defluorination may not occur. The uptakes of (+/-)-[18F]BMY 14802 and its enantiomers, (+)- and (-)-[18F]BMY 14802 in rat cerebellum, brain stem, hippocampus and spinal cord were similar and were significantly reduced by prior treatment of rat with haldol. This suggests that (+/-)-[18F]BMY 14802 and its enantiomers bind to sigma-receptors in a similar fashion.

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Positron-emission tomography is a unique imaging technique that has shown promise for improving staging, treatment planning, and monitoring of cancer. When used in conjunction with a radioactive glucose analog, positron-emission tomography has proven useful for detecting malignant tissue and quantitating changes in tumor glycolysis during and after treatment. This article reviews the principles of positron-emission tomography and its clinical role in cancer treatment.

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Positron emission tomography (PET) is a unique technique for imaging functional metabolism of normal and diseased tissue. Accelerated rate of glucose metabolism typical of malignant tumor cells can be detected by using fluorine-18 deoxyglucose. In this pilot study, PET FDG imaging was compared to computerized tomography for the pre-operative staging of colorectal carcinoma. We prospectively evaluated 16 patients by simultaneously performing PET FDG and CT imaging for lesions in the liver, colon and rectum. The results were compared to the operative findings in all patients. Twenty tumor sites (lymph nodes 5, colon and rectum 13, liver 2) were found on histology in 16 patients. On comparison with histology, sensitivity, specificity and predictive accuracy for detection of tumor sites were 90%, 66% and 87% with PET as compared to 60%, 100%, and 65% with CT. These findings represent increased sensitivity and predictive accuracy for staging of colorectal carcinoma with PET FDG imaging as compared to CT scanning.

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The normal range of Doppler findings in native kidneys has not been studied extensively. This study correlates changes in Doppler resistive index (RI) with age in patients without renal risk factors or renal disease. Young and old patients demonstrated the highest RI values (age < 1, mean RI = 0.73; age > 59, RI = 0.68), and patients in the 20-39 year age group showed the lowest values (RI = 0.59). The mean RI for all ages was 0.63. The cause of this variability is unknown. We suggest that age-related changes in Doppler values should be considered in the interpretation of renal Doppler measurements.

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OBJECTIVE: To compare thallium-201 (201Tl) myocardial perfusion imaging following intravenous adenosine and oral dipyridamole. DESIGN: Open-label, randomized, comparison. SETTING: Outpatient, university-affiliated clinic. PATIENTS: Fifteen patients with angiographically documented coronary artery disease. INTERVENTIONS: Planar 201Tl myocardial perfusion imaging following both intravenous adenosine 140 micrograms/kg/min for six minutes and oral dipyridamole suspension 300 mg. MAIN OUTCOME MEASURES: A comparison between adenosine and dipyridamole was made in the following areas: concordance in interpretation of 201Tl scintigrams, cardiac and noncardiac 201Tl uptake and clearance, hemodynamic and electrocardiographic changes, and adverse effects. RESULTS: The scintigraphic studies showed perfusion defects in 13 patients (87 percent) after dipyridamole and in 15 patients (100 percent) after adenosine. 201Tl uptake and clearance were quantitated in nine myocardial segments and in four extracardiac segments in each patient. 201Tl uptake was not significantly different between adenosine and dipyridamole studies in most cardiac regions. Extracardiac 201Tl uptake was significantly less in the liver and splanchnic regions following adenosine compared with dipyridamole. 201Tl clearance was not significantly different following adenosine and dipyridamole except in the anterolateral region in the anterior view. Hemodynamic changes following administration of intravenous adenosine and oral dipyridamole were not significantly different. Adverse effects were more common with adenosine than with dipyridamole. Adverse effects with adenosine were transient; however, adverse effects with dipyridamole were prolonged and required reversal with aminophylline in 2 patients. No patients required termination of the adenosine infusion or administration of aminophylline. CONCLUSIONS: These preliminary data suggest that adenosine 201Tl imaging may be a useful alternative to dipyridamole 201Tl imaging. Although adenosine produces more frequent adverse effects, they are generally better tolerated than those associated with dipyridamole.

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It is estimated that nearly one-third of solitary pulmonary nodules (SPNs) may represent bronchogenic carcinoma. The noninvasive imaging methods used currently (ie, plain radiography, computed tomography) are not reliable for accurate detection of malignancy in most SPNs. The authors prospectively evaluated use of positron emission tomography (PET) with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) for identification of malignancy in 20 patients with noncalcific, radiographically indeterminate SPNs. PET-FDG imaging demonstrated focal hypermetabolism in 13 biopsy-proved malignant nodules, whereas no increased FDG uptake was seen in the seven benign SPNs. Semiquantitative analysis with computation of differential uptake ratios also helped clearly differentiate benign nodules (mean +/- standard deviation, 0.56 +/- 0.27) from malignant nodules (mean +/- standard deviation, 5.63 +/- 2.38) (P less than .001). Thus, PET-FDG imaging may be a potentially useful noninvasive technique for accurate differentiation of benign and malignant SPNs that are radiographically indeterminate.

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Clinically oriented imaging with position emission tomography (PET) has come of age. Given an adequate referral base and physician interest, a compelling argument can be made at all levels of the review process for setting up a PET program in a clinical setting. PET is expensive. It is obvious that the cost of running a PET service depends heavily on an institution's ability to obtain reasonable financing. Educational institutions have the opportunity to acquire special funding through a variety of sources. On the other hand, money can be expensive for private entrepreneurs. It appears that in the near future PET centers will probably remain at educational institutions or large well-financed community hospitals able to raise money at reasonable rates until reimbursement issues are better resolved. Finally, the future of clinical PET may hinge significantly on the ability of commercial radiopharmaceutical suppliers to provide regional fluorodeoxyglucose distribution. As an institutional program development, PET offers opportunities by providing unique clinical data aiding the referral pattern. PET may serve as a magnet for recruitment in many areas and may promote interdisciplinary cooperation. A clinical PET center serves both as a model for future and more widespread use of PET and as a training ground for medical personnel. Finally, the unique capabilities of PET may facilitate grant opportunities.

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Because of its unique ability to demonstrate the metabolic consequences of myocardial ischemia, positron emission tomography (PET) is extremely valuable in assessing myocardial viability. PET imaging can identify the myocardial segments that are likely to improve after revascularization and may be more sensitive and specific for the detection of coronary artery disease compared with thallium perfusion imaging. Adenosine has several advantages over dipyridamole as a pharmacologic stress agent for use with PET. It produces maximal vasodilation in a significantly greater percentage of patients, is a more potent coronary vasodilator, and its very short half-life may be ideal for use with the very short half-life radioactive tracers used in PET. When combined with metabolic studies, adenosine may be useful for the assessment of patients who received thrombolytic therapy for an acute myocardial infarction.

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PET has a promising role in neuroradiology for accurate diagnosis and prognostication of malignant tumors as well as differential diagnosis of radiation necrosis and recurrent tumors. Particularly, PET has proven its ability to accurately differentiate radiation necrosis from recurrent brain tumor. Active tumors have accelerated glycolysis, and a remarkable accumulation of FDG radiotracer in high grade brain tumors is evident on PET images. Tumor metabolism also proportionally increases with increasing pathologic grades of brain tumor, and accelerated tumor metabolism indicates a poor prognosis for the tumor.

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Dynamic proctography is a radiographic procedure that has become widely used in the evaluation of pelvic floor function. The anorectal angle (ARA) is one parameter which is usually quantified during this examination. To determine the accuracy with which this measurement can be made, three physicians independently measured the resting and squeezing ARAs of 22 women. The coefficient of variation and the kappa statistic were used to describe the degree of agreement among the three examiners. These analyses revealed poor agreement among examiners for all 22 patients taken as individuals, (kappa less than or equal to 0.40; mean coefficient of variation at rest = 18 percent; mean coefficient during squeezing = 21 percent). These results suggest that measurements of ARAs will vary among examiners for any particular patient, even though individual examiners may demonstrate consistency in recording ARA data. There is wide interobserver variation in the measurement of the ARA from lateral radiographs, making quantification an exercise of only limited clinical value.

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