Intermittent dosing of axitinib combined with chemotherapy is supported by (18)FLT-PET in gastrointestinal tumours.

BACKGROUND: We evaluated week-on/week-off axitinib dosing plus chemotherapy in patients with gastrointestinal tumours, including tumour thymidine uptake by fluorine-18 3'-deoxy-3'-fluorothymidine positron emission tomography ((18)FLT-PET). METHODS: During a lead-in period, patients received twice daily (b.i.d.) axitinib 7 mg (n=3) or 10 mg (n=18) for 7 days followed by a 7-day dosing interruption; serial (18)FLT-PET scans were performed before day 1 and on days 7, 10, and 14. Axitinib plus FOLFIRI or FOLFOX was then administered in 2-week cycles; axitinib was interrupted on day 10 of each cycle for 7 days. RESULTS: The maximum tolerated dose of axitinib was 10 mg b.i.d., in a week-on/week-off schedule, combined with FOLFIRI or FOLFOX. Common all-causality grade 3 adverse events were neutropenia (38%), hypertension (33%), and fatigue (29%). Of 21 patients, 2 (10%) had a partial response and 12 (57%) had stable disease. Following 7 days of continuous axitinib dosing, tumour (18)FLT uptake decreased -49% from baseline and recovered to -28% and -17% from baseline, respectively, after 3 and 7 days of axitinib interruption. CONCLUSION: Axitinib administered in a week-on/week-off schedule combined with FOLFIRI or FOLFOX is supported by (18)FLT-PET data and was well tolerated in patients with gastrointestinal tumours.

FLAG chemotherapy followed by allogeneic stem cell transplant using nonmyeloablative conditioning induces regression of myelofibrosis with myeloid metaplasia.

A 38-year-old woman with agnogenic myeloid metaplasia complicated by the poor prognostic factors of severe osteosclerosis, prominent hepatosplenomegaly, and profound anemia was treated with FLAG chemotherapy to decrease her organomegaly before undergoing a nonmyeloablative allogeneic stem cell transplant from a matched-sibling donor. The patient's pre- and post transplant course were complicated by an autoimmune disorder and her post transplant course was complicated by severe hepatic and gastrointestinal GVHD. A technetium-99m sulfur colloid scan 4 months post transplant and bone marrow studies 8 months post transplant demonstrated intramedullary hematopoiesis, complete resolution of marrow fibrosis, and partial resolution of osteosclerosis.

The usefulness of F-18 deoxyglucose whole-body positron emission tomography (PET) for re-staging of renal cell cancer.

PURPOSE: The use of whole-body PET for re-staging of renal cell carcinoma has not been investigated. The aim of the current study was to examine the diagnostic accuracy and clinical usefulness of whole-body PET imaging for re-staging of renal cell cancer. PATIENTS AND METHODS: Clinical PET was performed for re-staging in 36 patients with advanced renal cell cancer. Written reports of imaging studies (including CT, MRI, US, plain film and bone scan), patient history, and extensive chart notes were used to define the clinical stage before PET (pre-PET stage). The written PET report was used to define the clinical stage after PET (PET stage). Reports were used to determine the accuracy of PET for re-staging renal cell cancer and for defining biopsy proven lesions. Clinical parameters and biopsy proven lesions served as reference for the accuracy of PET for re-staging renal cell cancer. RESULTS: PET classified the clinical stage correctly in 32/36 patients (89%) and was incorrect in 4/36 (11%) (sensitivity and specificity: 87% and 100%). In 20 patients, 25 suspicious lesions were biopsied within 3.2 +/- 6.7 months of the PET study. Of these, 17 were malignant and 8 were benign. PET correctly classified 21/25 (84%) of the biopsied lesions (sensitivity and specificity: 88% and 75%). CONCLUSION: PET re-stages renal cell cancer with a diagnostic accuracy of 89%. Its diagnostic accuracy for classifying biopsy proven anatomic lesions as malignant or benign was 84%. These findings suggest that PET is useful in characterizing anatomic lesions of unknown significance in patients with renal cell cancer.

Positron emission tomography in evaluation of dementia: Regional brain metabolism and long-term outcome.

CONTEXT: Deficits in cerebral glucose utilization have been identified in patients with cognitive dysfunction attributed to various disease processes, but their prognostic and diagnostic value remains to be defined. OBJECTIVE: To assess the sensitivity and specificity with which cerebral metabolic patterns at a single point in time forecast subsequent documentation of progressive dementia. DESIGN, SETTING, AND PATIENTS: Positron emission tomography (PET) studies of [(18)F]fluorodeoxyglucose in 146 patients undergoing evaluation for dementia with at least 2 years' follow-up for disease progression at the University of California, Los Angeles, from 1991 to 2000, and PET studies in 138 patients undergoing evaluation for dementia at an international consortium of facilities, with histopathological diagnoses an average of 2.9 years later, conducted from 1984 to 2000. MAIN OUTCOME MEASURES: Regional distribution of [(18)F]fluorodeoxyglucose in each patient, classified by criteria established a priori as positive or negative for presence of a progressive neurodegenerative disease in general and of Alzheimer disease (AD) specifically, compared with results of longitudinal or neuropathologic analyses. RESULTS: Progressive dementia was detected by PET with a sensitivity of 93% (191/206) and a specificity of 76% (59/78). Among patients with neuropathologically based diagnoses, PET identified patients with AD and patients with any neurodegenerative disease with a sensitivity of 94% and specificities of 73% and 78%, respectively. The negative likelihood ratio of experiencing a progressive vs nonprogressive course over the several years following a single negative brain PET scan was 0.10 (95% confidence interval, 0.06-0.16), and the initial pattern of cerebral metabolism was significantly associated with the subsequent course of progression overall (P<.001). CONCLUSION: In patients presenting with cognitive symptoms of dementia, regional brain metabolism was a sensitive indicator of AD and of neurodegenerative disease in general. A negative PET scan indicated that pathologic progression of cognitive impairment during the mean 3-year follow-up was unlikely to occur.

[(99m)Tc]MAG(3)-mannosyl-dextran: a receptor-binding radiopharmaceutical for sentinel node detection.

Technetium-99m-labeled benzoyl-mercaptoacetylglycylglycyl-glycine-mannosyl-dextran ([(99m)Tc]MAG(3)-mannosyl-dextran) is a receptor-binding radiotracer that binds to mannose-binding protein, a receptor expressed by recticuloendothelial tissue. This agent is composed of a 10.5-kilodalton molecule of dextran and multiple units of mannose, and benzoyl-mercaptoacetylglycylglycyl-glycine (BzMAG(3)). The tetraflorophenol-activated ester of BzMAG(3) and the imidate of thiomannose were used to covalently attach BzMAG(3) and mannose to an amino-terminated conjugate of dextran. This yielded a 19-kilodalton macromolecule consisting of 3 BzMAG(3) and 21 mannose units per dextran. Dynamic light scattering was used to measure a mean diameter of 5.5 nanometers for BzMAG(3)-mannosyl-dextran and 0.28 microns for filtered Tc-99m sulfur colloid. A preliminary sentinel node detection study employing right fore and hind footpad injections of [(99m)Tc]MAG(3)-mannosyl-dextran and left fore and hind footpad injections of filtered Tc-99m sulfur colloid demonstrated greater sentinel lymph node uptake by the receptor-binding agent.

A synthetic macromolecule for sentinel node detection: (99m)Tc-DTPA-mannosyl-dextran.

UNLABELLED: We report the synthesis and preliminary biologic testing of a synthetic macromolecule, (99m)Tc-diethylenetriaminepentaacetic acid (DTPA)--mannosyl-dextran, for sentinel node detection. METHODS: Synthesis started with a 2-step process that attaches a high density of amino-terminated leashes to a dextran backbone. Allyl-bromide was reacted with pharmaceutical-grade dextran to yield allyl-dextran. After diafiltration with water, filtration, and lyophilization, the product was reacted with aminoethanethiol and ammonium persulfate. The resulting amino-conjugated dextran was dialyzed, filtered, and lyophilized. The mixed anhydride method was used to attach DTPA; after dialysis, filtration, and lyophilization, 2-imino-2-methoxyethyl-1-D-mannose was used to attach the receptor substrate. The molecular diameter was measured by dynamic light scattering. Amino, mannose, and DTPA densities were measured by trinitrobenzene sulfonate assay, sulfuric acid/phenol assay, and inductively coupled plasma spectroscopy of gadolinium-DTPA-mannosyl-dextran, respectively. Receptor affinity was measured by Scatchard assay of rabbit liver. Axillary, popliteal, and iliac lymph nodes and each injection site were assayed for radioactivity at 1 and 3 h after injection of approximately 3.7 MBq (0.050 mL) (99m)Tc-DTPA-mannosyl-dextran (0.22 nmol) or filtered (99m)Tc-sulfur colloid into the foot pads. Four animals were studied at each time point. RESULTS: DTPA-mannosyl-dextran had a molecular weight of 35,800 g/mol and a molecular diameter of 7.1 nm. The final amine, mannose, and DTPA densities were 23, 55, and 8 mol per dextran. Labeling yields were in excess of 98% and stable for 6 h. Specific activities of 74 x 10(6) GBq/mol were achieved. The equilibrium dissociation constant for binding to the mannose-terminated glycoprotein receptor was 0.12 +/- 0.07 nmol/L. The popliteal extraction at both 1 h and 3 h was significantly (P < 0.05) higher for (99m)Tc-DTPA-mannosyl-dextran (90.1% +/- 10.7% and 97.7% +/- 2.0%, respectively) than for filtered (99m)Tc-sulfur colloid (78.8 +/- 6.5 and 67.4% +/- 26.8%, respectively). (99m)Tc-DTPA-mannosyl-dextran exhibited significantly faster injection site clearance than did filtered (99m)Tc-sulfur colloid. The (99m)Tc-DTPA-mannosyl-dextran percentage injected dose (%ID) for the front and rear paws was 52.6 +/- 10.5 and 52.3 +/- 8.0 at 1 h and 45.7 +/- 8.5 and 43.6 +/- 8.2 at 3 h after administration. The filtered (99m)Tc-sulfur colloid %ID for the front and rear paws was 70.4 +/- 11.0 and 66.3 +/- 15.1 at 1 h and 55.5 +/- 7.8 and 66.9 +/- 8.5 at 3 h. Lymph node accumulation of each agent at either 1 or 3 h was not significantly different. CONCLUSION: (99m)Tc-DTPA-mannosyl-dextran is a receptor-based sentinel node radiotracer that exhibits the desired properties of rapid injection site clearance and low distal node accumulation. This molecule is the first member of a new class of diagnostic agents based on a macromolecular backbone with a high density of sites for the attachment of substrates and imaging reporters.

Exaggerated muscle mechanoreflex control of reflex renal vasoconstriction in heart failure.

In heart failure (HF) patients, reflex renal vasoconstriction during exercise is exaggerated. We hypothesized that muscle mechanoreceptor control of renal vasoconstriction is exaggerated in HF. Nineteen HF patients and nineteen controls were enrolled in two exercise protocols: 1) low-level rhythmic handgrip (mechanoreceptors and central command) and 2) involuntary biceps contractions (mechanoreceptors). Renal cortical blood flow was measured by positron emission tomography, and renal cortical vascular resistance (RCVR) was calculated. During rhythmic handgrip, peak RCVR was greater in HF patients compared with controls (37 +/- 1 vs. 27 +/- 1 units; P < 0.01). Change in (Delta) RCVR tended to be greater as well but did not reach statistical significance (10 +/- 1 vs. 7 +/- 0.9 units; P = 0.13). RCVR was returned to baseline at 2-3 min postexercise in controls but remained significantly elevated in HF patients. During involuntary muscle contractions, peak RCVR was greater in HF patients compared with controls (36 +/- 0.7 vs. 24 +/- 0.5 units; P < 0.0001). The Delta RCVR was also significantly greater in HF patients compared with controls (6 +/- 1 vs. 4 +/- 0.6 units; P = 0.05). The data suggest that reflex renal vasoconstriction is exaggerated in both magnitude and duration during dynamic exercise in HF patients. Given that the exaggerated response was elicited in both the presence and absence of central command, it is clear that intact muscle mechanoreceptor sensitivity contributes to this augmented reflex renal vasoconstriction.

Exaggerated renal vasoconstriction during exercise in heart failure patients.

BACKGROUND: During static exercise in normal healthy humans, reflex renal cortical vasoconstriction occurs. Muscle metaboreceptors contribute importantly to this reflex renal vasoconstriction. In patients with heart failure, in whom renal vascular tone is already increased at rest, it is unknown whether there is further reflex renal vasoconstriction during exercise. METHODS AND RESULTS: Thirty-nine heart failure patients (NYHA functional class III and IV) and 38 age-matched control subjects (controls) were studied. Renal blood flow was measured by dynamic positron emission tomography. Graded handgrip exercise and post-handgrip ischemic arrest were used to clarify the reflex mechanisms involved. During sustained handgrip (30% maximum voluntary contraction), peak renal vasoconstriction was significantly increased in heart failure patients compared with controls (70+/-13 versus 42+/-1 U, P=0.02). Renal vasoconstriction returned to baseline in normal humans by 2 to 5 minutes but remained significantly increased in heart failure patients at 2 to 5 minutes and had returned to baseline at 20 minutes. In contrast, during post-handgrip circulatory arrest, which isolates muscle metaboreceptors, peak renal vasoconstriction was not greater in heart failure patients than in normal controls. In fact, the increase in renal vasoconstriction was blunted in heart failure patients compared with controls (20+/-5 versus 30+/-2 U, P=0.05). CONCLUSIONS: During sustained handgrip exercise in heart failure, both the magnitude and duration of reflex renal vasoconstriction are exaggerated in heart failure patients compared with normal healthy humans. The contribution of the muscle metaboreceptors to reflex renal vasoconstriction is blunted in heart failure patients compared with normal controls.

Comparison of helical computerized tomography, positron emission tomography and monoclonal antibody scans for evaluation of lymph node metastases in patients with prostate specific antigen relapse after treatment for localized prostate cancer.

PURPOSE: We compare the detection of metastatic disease by helical computerized tomography (CT), positron emission tomography (PET) with F-18 fluorodeoxyglucose and monoclonal antibody scan with 111indium capromab pendetide in patients with an elevated prostate specific antigen (PSA) after treatment for localized prostate cancer. MATERIALS AND METHODS: A total of 45 patients with an elevated PSA (median 3.8 ng./ml.) were studied following definitive local therapy with radical prostatectomy in 33, radiation therapy in 9 and cryosurgery in 3. CT of the abdomen and pelvis, and whole body PET were performed in all patients, of whom 21 also underwent monoclonal antibody scan. Lymph nodes 1 cm. in diameter or greater on CT were considered abnormal and were sampled by fine needle aspiration in 12 patients. RESULTS: PET and CT were positive for distant disease in 50% of 22 patients with PSA greater than 4, and in 4 and 17%, respectively, of 23 with PSA less than 4 ng./ml. The detection rate for metastatic disease was similar for CT and PET, and higher overall than that for monoclonal antibody scan. Monoclonal antibody scan was true positive in only 1 of 6 patients, while PET was true positive in 6 of 9 with CT guided fine needle aspiration proved metastases. CONCLUSIONS: CT and PET each detected evidence of metastatic disease in 50% of all patients with a high PSA or PSA velocity (greater than 4 ng./ml. or greater than 0.2 ng./ml. per month, respectively). Both techniques are limited for detecting metastatic disease in patients with a low PSA or PSA velocity. Our data suggest that monoclonal antibody scan has a lower detection rate than CT or PET.

Quantification of myocardial blood flow using 13N-ammonia and PET: comparison of tracer models.

UNLABELLED: Several tracer kinetic methods have been proposed for quantification of regional myocardial blood flow (MBF) with 13N-ammonia and PET. Merits and limitations specific to each approach, however, generally are not clear, because they have not been evaluated in the same experimental environment. Therefore, we compared six different commonly used methods (11 modifications) to characterize the accuracy of each approach. The methods included the two-parameter model (method 1), the modified two-parameter model (method 2), the four-parameter model (method 3), the graphical analysis (method 4), the first-pass extraction method (method 5) and the dose uptake index (DUI; method 6). METHODS: Eleven studies in four dogs, 16 studies in eight healthy human volunteers and 14 studies in seven patients were performed using 13N-ammonia and PET. MBF in dogs was varied with dipyridamole and coronary occlusions and was measured independently and simultaneously with microspheres. Volunteers and patients were studied at baseline and after dipyridamole. MBF and DUI were estimated using a time-activity curve (Qi[t]) derived from dynamic images and regions of interest (ROls) and using the six methods. DUI was defined as Qi(t = 2 min) x weight/dose. RESULTS: MBF estimated by methods 1-5 correlated well with microsphere MBF in dogs. MBF estimates by method 1 correlated well with those by methods 2, 4 and 5 and to a lesser degree with those by method 3 in both dog and human studies. DUI correlated poorly with MBF by microspheres and by methods 1-5 in both dog and human studies. MBF estimates by method 3 showed larger dispersion (SD/mean flow) and higher sensitivity to metabolites correction in arterial blood than those by methods 1, 2, 4 and 5. CONCLUSION: MBF can be measured accurately using 13N-ammonia PET and tracer kinetic methods. DUI is a poor indicator of MBF values. The results indicate that preference should be given to the two-parameter model, incorporating geometrical ROI representation (method 2) among the compartment models, and to the graphical analysis (method 4) among the noncompartmental approaches.

Blood flow-metabolism imaging with positron emission tomography in patients with diabetes mellitus for the assessment of reversible left ventricular contractile dysfunction.

OBJECTIVES: The purpose of this study was to evaluate the predictive accuracy of positron emission tomography (PET) blood flow-F-18 fluorodeoxyglucose (FDG) imaging in coronary artery disease (CAD) patients with diabetes mellitus (DM). BACKGROUND: Positron emission tomography accurately predicts the postrevascularization improvement in left ventricular dysfunction in unselected patients with CAD. In diabetic patients, however, poor myocardial glucose utilization may limit the accuracy of the approach. METHODS: Forty patients (64+/-10 years old; 19 with DM = group I; 21 without DM = group II) with reduced left ventricular ejection fraction (LVEF = 29+/-6%) were studied with N-13 ammonia and FDG PET before coronary revascularization. Studies were performed after intravenous injection of regular insulin (group I) or oral glucose administration (group II). Blood flow-FDG mismatches and matches were identified by polar map analysis in the three vascular territories of the left anterior descending, left circumflex and right coronary artery. Wall motion and LVEF were assessed by two-dimensional echocardiography before and 158+/-123 days after revascularization. RESULTS: Of 107 vascular territories analyzed, 46 were classified as mismatch, 29 as match and 32 as normal. The FDG image quality, assessed by F-18 myocardium to blood pool activity ratios, and the predictive accuracy were similar in both groups; presence of a blood flow/FDG mismatch had a sensitivity of 92% (group I) and 94% (group II) and a specificity of 85% (group I) and 79% (group II) for an improvement in regional left ventricular function. A postrevascularization improvement in global left ventricular function was related to the extent of blood flow/FDG mismatch; LVEF increased from 30+/-7% to 35+/-7% (p = 0.017) in patients with one mismatch and from 27+/-4% to 41+/-7% (p < 0.001) in those with two mismatches. CONCLUSIONS: The predictive accuracy of blood flow/FDG imaging is maintained in patients with DM when a clinically acceptable study protocol, which guarantees good FDG image quality, is used. The extent of a blood flow/metabolism mismatch is correlated with the magnitude of the postrevascularization improvement in global left ventricular function.

Radioaerosol scintigraphy in infants and children born to mothers with HIV disease. Pediatric Pulmonary and Cardiovascular Complications (of Vertically Transmitted Human Immunodeficiency Virus) Study Group.

PURPOSE: To determine the usefulness of technetium 99m diethyltriaminepentacetic acid (DTPA) radioaerosol inhalation-clearance scintigraphy for early detection of pulmonary complications of human immunodeficiency virus (HIV) disease in children. MATERIALS AND METHODS: A total of 301 studies were performed in 132 HIV-positive children (group 1; mean age, 46.6 months). In children born to HIV-positive mothers (group 2), 273 studies were performed in 160 children who eventually were proved to be HIV negative (mean age, 10.3 months), and 80 studies were performed in 47 HIV-positive children (mean age, 15.6 months). Radioaerosol studies were performed by using commercially available radioaerosol nebulizers. Pulmonary clearance half-time was measured by using conventional gamma camera computer systems. Radioaerosol results were correlated with indexes of pulmonary health and function. RESULTS: The HIV-negative, group 2 children had a mean radioaerosol clearance half-time (58.1 minutes; 162 studies in 108 children) similar to that reported in healthy adults. Group 1 children with pulmonary involvement exhibited a faster mean clearance half-time (28.6 minutes) than did children without evidence of pulmonary involvement from either group 1 or group 2 (P < .05). A faster pulmonary clearance rate did not simply reflect the presence of chest disease that also was detectable on radiographs (P = .3). CONCLUSION: Quantitative DTPA radioaerosol clearance studies may provide useful information about pulmonary involvement in selected children with HIV disease.

18-FDG imaging in breast cancer.

Despite the large number of women with breast cancer and the importance of this disease in health care, only a relatively small number of published reports involve the application of 18-fluorodeoxyglucose (FDG) in the evaluation of patients with breast cancer. This report summarizes the results of these studies, presents the opinions from various clinical oncologists from both a university and community setting, and discusses the possible future implication of positron imaging technology in the management of breast cancer. The four potential areas of clinical application include (1) detection and differentiation of primary breast lesions, (2) staging of axillary lymph nodes, (3) detection of residual and metastatic disease, and (4) monitoring the response to chemotherapy.

ROC and localization ROC analyses of lesion detection in whole-body FDG PET: effects of acquisition mode, attenuation correction and reconstruction algorithm.

UNLABELLED: Receiver operating characteristic (ROC) and localization ROC (LROC) studies were performed to compare lesion detection at the borderline of detectability on images reconstructed with two-dimensional filtered backprojection (FBP) without attenuation correction (a common clinical protocol), three-dimensional FBP without attenuation correction, two-dimensional FBP with segmented attenuation correction and a two-dimensional iterative maximum a posteriori (MAP) algorithm using attenuation correction. Lung cancer was the model for the study because of the prominent role of 18F-fluorodeoxyglucose PET in the staging of lung cancer and the importance of lesion detection for staging. METHODS: Simulated lung cancer lesions were added to two-dimensional and three-dimensional PET data from healthy volunteers. Data were reconstructed using the four methods. Four nuclear medicine physicians evaluated the images. Detection performance with each method was compared using ROC and LROC analysis. Jackknife analysis provided estimates of statistical significance for differences across all readers for the ROC results. RESULTS: ROC and LROC results indicated statistically significant degradation in detection performance with three-dimensional acquisition (average area under ROC curves [Az] 0.51; average area under LROC curves [A(z,LROC)] 0.13) and segmented attenuation correction (average Az 0.59; average Az,LROC 0.29) compared with two-dimensional FBP without attenuation correction (average Az 0.79; average A(z,LROC) 0.54). ROC and LROC results indicated an improvement in detection performance with iterative MAP reconstruction (average Az 0.83; average A(z,LROC) 0.64) compared with two-dimensional FBP reconstruction; this improvement was not statistically significant. CONCLUSION: Use of segmented attenuation correction or three-dimensional acquisition with FBP reconstruction is not expected to improve detection of lung lesions on whole-body PET images compared with images with two-dimensional FBP without attenuation correction. The potential improvement in detection obtained with an iterative MAP reconstruction method is small compared with that obtained with two-dimensional FBP without attenuation correction.

Positron emission tomography as a diagnostic tool in oncology.

Early diagnosis in oncology is important for treatment by surgical intervention, which generally has the highest curative potential. For higher stages of disease involvement, initiation of rapid treatment is indicated to provide the patient with the optimal therapy regimen. Although this may not improve the prognosis, it will maintain the quality of life. Anatomic imaging modalities, such as CT, MR imaging, and US, are clinically important high-resolution imaging techniques that are well suited to reveal structural abnormalities. However, the differentiation of lesions as being benign or malignant is still problematic. Metabolic imaging modalities in nuclear medicine (NM), i.e., single photon emission computed tomography (SPECT) and positron emission tomography (PET), can reveal biochemical parameters of the lesions such as glucose, oxygen, or amino acid metabolism, or measure the receptor density status. These parameters may allow a completely new clinical perspective in the management and understanding of diseases such as cancer. Although PET has been around since the early 1960s, it has only recently emerged as a powerful diagnostic tool in oncology. Society has great difficulty accepting this clinical imaging modality because of its high cost and complexity. Current applications of PET in oncology have been in characterizing lesions, differentiating recurrent disease from treatment effects, staging tumors, evaluating the extent of disease, and therapy monitoring. Here, the role of PET in diagnosis, staging, and restaging of cancer is reviewed and compared with the other tumor imaging modalities. We cover articles published in the past 3 years. We utilize the typical radiology format, in which the contribution in each body area is reviewed (topographic orientation), instead of the more organ-based approach used in internal medicine.

Positron emission tomography in urological oncology.

PURPOSE: We provide scientists and clinicians with an introduction to the basic principles and methods of positron emission tomography (PET) and summarize the recent research and clinical applications of PET in the urological field. Specifically, we introduce PET so that the reader can understand and objectively review current and future articles that involve this imaging technology. MATERIALS AND METHODS: The recent applications of PET in urology in the published literature were searched and reviewed. RESULTS: In prostate carcinoma preliminary studies using radiotracer 18-fluoro-2-deoxyglucose (FDG) demonstrated that PET cannot reliably differentiate between primary prostate cancer and benign prostatic hyperplasia, and that PET is not as sensitive as bone scintigraphy for the detection of osseous metastases. However, PET may have a role in the detection of lymph node metastases in patients with prostate specific antigen relapse after primary local therapy. In renal cell carcinoma recent studies have shown the ability of FDG PET to detect primary and metastatic lesions and to monitor response to therapy. In the staging of testicular cancer FDG PET has been used to differentiate viable carcinoma from benign teratomas and/or fibrotic or necrotic changes. CONCLUSIONS: Current developments in PET technology that accurately stage the extent of tumor before surgery as well as monitor effectiveness or ineffectiveness of new or current therapies may make PET a valuable tool in research and in the management of urological diseases.

Evaluating tumor biology and oncological disease with positron-emission tomography.

The usefulness of positron-emission tomography (PET) for noninvasive assessment of several biological parameters of neoplastic tissue has been reviewed. Numerous radiotracers have been developed, whose particular distribution in the presence of cancer in vivo serves to distinguish medically relevant properties of the tumor cells with which they associate. That distribution is most accurately determined through use of a PET scanner, to localize and quantify the tracer molecules, in which have been incorporated positron-emitting isotopes. These tracers include hypoxia markers, receptor ligands, substrates for enzymatic modification by the products of expression of specific genes, and precursors of protein anabolism and carbohydrate catabolism. In addition, application of PET to evaluation of patients with some particular cancers has been examined, while placing special emphasis on the level of scientific rigor of the evidence underlying conclusions about appropriate use of PET in oncology.

Analytical decision model for the cost-effective management of solitary pulmonary nodules.

PURPOSE AND METHODS: Multiple strategies are currently being used to manage patients who present with indeterminate solitary pulmonary nodules (SPN). We have used decision-analysis models to assess the cost-effectiveness of various strategies for the diagnosis and management of SPN. Four decision strategies were compared: a wait and watch strategy, a surgery strategy, a computed tomography (CT)-based strategy, and a CT-plus-positron emission tomography (PET) strategy. An incremental cost-effectiveness ratio (ICER) was used to compare all strategies to the wait and watch strategy. RESULTS: A CT-plus-PET strategy was the most cost-effective over a large pretest likelihood (probability of having a malignant nodule), with a range of 0.12 to 0.69. Furthermore, within this likelihood range, the potential cost savings of using the CT-plus-PET strategy over the CT strategy ranged from $91 to $2,200 per patient. This translates to a yearly national savings of approximately $62.7 million. CONCLUSION: Decision-analysis modeling indicates the potential cost-effectiveness of [18F]2-fluoro-2-deoxy-D-glucose (FDG)-PET in the management of SPN. Furthermore, the decision trees developed can be used to model various features of the management of SPN, including modeling the cost-effectiveness of other newly emerging technologies.

Noninvasive methods for quantitating blood time-activity curves from mouse PET images obtained with fluorine-18-fluorodeoxyglucose.

UNLABELLED: The mouse model is currently being explored for various applications with PET imaging. Low resolution of current animal scanners relative to mouse size leads to difficulty in quantitating data from mouse PET images. We have, therefore, investigated methods for determining blood time-activity curves (TACs) from mouse PET studies done with fluorine-18-fluorodeoxyglucose (FDG). METHODS: Eight mice were fasted, the tail vein was injected with 150-300 microCi of FDG and dynamic images were acquired with a CTI/Siemens (Knoxville, TN) animal tomograph for 64.5 min. Concurrently, 11-14 left ventricle (LV) blood samples were drawn directly from the LV chamber. Organ TACs were obtained by drawing circular regions of interest (ROIs) of various sizes on images of the heart, liver and brain. For each mouse, the FDG model parameter K = (K1 x k3)/(k2 + k3) was estimated by a Patlak algorithm with various estimates of the blood TAC and, as a reference tissue TAC, the brain TAC. RESULTS: Most partial-volume-corrected heart ROI TACs overestimated the LV samples. Blood TACs from heart images produced statistically different estimates of K than did the LV samples. The liver image-derived blood TACs yielded estimates of K that were comparable to those yielded by the LV samples. Estimates of K determined with two directly sampled LV points in conjunction with the liver image-derived TAC were not statistically different from the estimates obtained with the LV samples. The size and location of ROIs on images of the liver minimally affected the TACs. CONCLUSION: We have shown that it is experimentally possible to obtain a blood TAC from mouse studies by repeatedly sampling from the LV. We have also shown that images of the liver can be used to reliably estimate the blood TAC. Future FDG PET studies with the mouse model will benefit from this demonstrated ability to noninvasively quantitate blood TACs directly from FDG PET images.