fluoro-2-deoxy-D-glucose Uptake Research Articles

Chemotherapy-Induced Normalization of FDG Uptake by Colorectal Liver Metastases Does Not Usually Indicate Complete Pathologic Response

Dramatic responses are being observed in colorectal cancer liver metastases treated with newer chemotherapeutic regimens. These have been associated with normalization of [18F]fluoro-2-deoxy-d-glucose (FDG) uptake (complete metabolic response) on follow-up Positron Emission Tomography with [18F]fluoro-2-deoxy-d-glucose (FDG-PET) scans in some patients. It is unclear how often complete metabolic response is indicative of complete tumor destruction. We analyzed a subset of patients who had neoadjuvant chemotherapy for hepatic metastases from colorectal adenocarcinoma. Inclusion criteria were: (1) FDG-avid hepatic lesions before initiation of chemotherapy; (2) complete metabolic response of the same lesions after chemotherapy; and (3) histopathologic examination of hepatic lesions. Complete pathologic response was defined as no histologically identifiable viable tumor. Fourteen patients fit the inclusion criteria. All had synchronous, hepatic-only colorectal metastases. On microscopic examination, complete pathologic response to the neoadjuvant regimen was found in only 5 of 34 lesions (15%) and in only 3 of the 14 patients (21%). Seven lesions had complete metabolic response and disappeared on computed tomography (CT); of these, six still contained viable tumor. We conclude that complete metabolic response on FDG-PET after neoadjuvant chemotherapy is an unreliable indicator of complete pathologic response. Therefore, currently, curative resection of liver metastases in these patients should not be deferred on the basis of FDG-PET findings.

Cellular metabolic responses of PET radiotracers to 188Re radiation in an MCF7 cell line containing dominant-negative mutant p53

We investigated the relations between the cell uptakes of metabolic radiotracers and beta-radiation pretreatment using a dominant mutant p53 (p53mt) cell line to evaluate the effects of p53 genes on (18)F labeled positron emission tomography (PET) radiotracer uptakes. pCMV-Neo-Bam (control), which contains a neo-resistance marker, and p53 dominant-negative mutant expression constructs were stably transfected into MCF7 cell line. Cells were plated in 24-well plates at 1.0x10(5) cells for 18 h. Rhenium-188 ((188)Re) (a beta emitter) was added to the medium (3.7, 18.5, 37 MBq) and incubated for 24 h. We performed gamma-counting to determine the cellular uptakes of 2-[(18)F]fluoro-2-deoxy-d-glucose (FDG), o-(2-[(18)F]fluoroethyl)-l-tyrosine (FET) and 2'-[(18)F]fluoro-2'-deoxythymidine (FLT) (370 kBq, 60 min). Cell viabilities were determined by trypan blue staining and flow cytometry. p53mt cells showed 1.5-2-fold higher FDG uptake than wild-type p53 cells in basal condition, and the difference of FDG uptake was greater after (188)Re treatment (P<.01). FET uptake increased with (188)Re dose without a significant difference between p53 statuses. p53mt cells showed lower FLT uptake than wild-type p53 cells in basal condition, and the difference of FLT uptake was greater after (188)Re treatment. By cell viability testing and FACS analysis, p53mt cells showed lower viability and a larger apoptotic fraction (sub-G1) than wild-type p53 cells after (188)Re treatment. We speculate that p53 dysfunction increases glucose and decreases thymidine metabolism in cancer cells and that this may be exaggerated by (188)Re beta-radiation. Our findings suggest that FDG could reflect tumor viability and malignant potential after (188)Re beta-radiation treatment, whereas FLT could be a more useful PET radiotracer for assessing therapeutic response to beta-radiation, especially in cancer cells with an altered function of p53.

2-[ 18F]-Fluoro-2-deoxy- d-glucose positron emission tomography as guidance for primary treatment in patients with advanced-stage resectable squamous cell carcinoma of the larynx and hypopharynx

Background High uptake of 2-[ 18F]-fluoro-2-deoxy- d-glucose (FDG) is associated with unfavorable results. Pretreatment FDG uptake was evaluated as a predictor of survival and guidance for primary surgery or radiotherapy (RT) in patients with squamous cell carcinoma (SCC) of the larynx and hypopharynx. Materials and methods Seventy-nine consecutive patients with newly diagnosed advanced resectable SCC of the larynx and hypopharynx underwent FDG positron emission tomography (PET) before surgical resection plus RT and chemotherapy (surgery group, n = 40) or RT with chemotherapy and surgical salvage (RT group, n = 39). Age, tumor stage, histological grade, treatment strategy, and standardized uptake value (SUV) were analyzed for association with local control and survival. Results Overall local control and survival in the two groups did not differ ( P > 0.1). In univariate analysis, nodal positivity ( P = 0.014) and SUV > 8.0 ( P = 0.007) were associated with poorer disease-free survival (DFS). In multivariate analysis, SUV remained an independent determinant of DFS ( P = 0.014). When patients with SUV > 8.0 in the two treatment groups were analyzed separately, those in the surgery group tended to have a higher 3-year DFS than those in the RT group, despite no statistical significance (48% vs. 27%, P = 0.085). Conclusions High FDG uptake is associated with poor survival in patients with advanced laryngopharyngeal SCC. Patients with high FDG uptake may be better treated by surgical resection followed by RT and chemotherapy.

Monitoring chemotherapeutic response in RIF-1 tumors by single-quantum and triple-quantum-filtered 23Na MRI, 1H diffusion-weighted MRI and PET imaging

The effects of 5-fluorouracil (5FU, 150 mg/kg, ip) on subcutaneously implanted radiation-induced fibrosarcoma (RIF-1) tumors were monitored by in vivo (1)H MRI to evaluate the water apparent diffusion coefficient (ADC), by single-quantum (SQ) and triple-quantum-filtered (TQF) (23)Na MRI to evaluate compartmental Na(+) content and by positron emission tomography (PET) to evaluate 2-[(18)F]fluoro-2-deoxy-d-glucose (FDG) uptake in the tumor. The MRI experiments were performed on untreated control and treated mice once before and then daily for 3 days after treatment. The PET experiments were performed on separate groups of age- and tumor-volume-matched animals once before and then 3 days after treatment. Tumor volumes significantly decreased in treated animals 2 and 3 days posttreatment. At the same time points, in vivo MRI measurements showed an increase in both total tissue SQ (23)Na signal intensity (SI) and water ADC in treated tumors while control tumors showed no change in these parameters. TQF (23)Na SI and FDG uptake were significantly lower in treated tumors compared with control tumors 3 days after 5FU treatment. The correlated increases in total tissue (23)Na SI and water ADC following chemotherapy reflect an increase in extracellular space, while the lower TQF (23)Na SI and FDG uptake in treated tumors compared with control tumors suggest a shift in tumor metabolism from glycolysis to oxidation and/or a decrease in cell density.

Bowel Hot Spots at PET-CT

Positron emission tomography (PET) with 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) has been shown to be sensitive in the detection of many bowel malignancies, but its specificity is lower because of various physiologic and pathologic patterns of bowel FDG uptake. PET-computed tomography (CT) can be useful in localizing and characterizing foci of increased FDG uptake within the bowel. As the use of PET-CT in the staging and monitoring of oncologic disease continues to expand, familiarity with these patterns of bowel FDG uptake is essential and can help determine the need for and the relative urgency of further testing. Although a variety of imaging protocols are used for PET-CT, the use of negative oral contrast agent allows improved bowel distention while eliminating potential artifacts caused by high-density oral contrast agents. In addition, correlation with the CT portion of the combined PET-CT examination can sometimes help identify the cause of focal or segmental bowel uptake. The radiologist should be aware of potential pitfalls in the evaluation of FDG-avid foci within the abdomen, including bowel motility and low-attenuation lesions mimicking bowel. Nevertheless, even though the precise role of combined PET-CT for bowel assessment has yet to be determined, the application of sound basic principles of image interpretation will help ensure the accurate interpretation of bowel findings seen with this combined modality.

Successful high-resolution animal positron emission tomography of human Ewing tumours and their metastases in a murine xenograft model

As primary osseous metastasis is the main adverse prognostic factor in patients with Ewing tumours, a NOD/scid mouse model for human Ewing tumour metastases has been established to examine the mechanisms of metastasis. The aim of this study was to evaluate the feasibility of diagnostic molecular imaging by small animal PET in this mouse model. Human Ewing tumour cells were transplanted into immune-deficient NOD/scid mice via s.c injection (n=17) or i.v. injection (n=17). The animals (mean weight 23.2 g) were studied 2-7 weeks after transplantation using a submillimetre resolution animal PET scanner. To assess glucose utilisation and bone metabolism, mice were scanned after intravenous injection of 9.6 MBq (mean) 2-[(18)F]fluoro-2-deoxy-D: -glucose (FDG) or 9.4 MBq (mean) [(18)F]fluoride. Whole-body PET images were analysed visually and semi-quantitatively [%ID/g, tumour to non-tumour ratio (T/NT)]. Foci of pathological uptake were identified with respect to the physiological organ uptake in corresponding regions. Subcutaneously transplanted Ewing tumours demonstrated a moderately increased glucose uptake (median %ID/g 2.5; median T/NT 2.2). After i.v. transplantation, the pattern of metastasis was similar to that in patients with metastases in lung, bone and soft tissue. These metastases showed an increased FDG uptake (median %ID/g 3.6; median T/NT 2.7). Osseous metastases were additionally visible on [(18)F]fluoride PET by virtue of decreased [(18)F]fluoride uptake (osteolysis; median %ID/g 8.4; median T/NT 0.59). Metastases were confirmed immunohistologically. Diagnostic molecular imaging of Ewing tumours and their small metastases in an in vivo NOD/scid mouse model is feasible using a submillimetre resolution PET scanner.

Radionuclide imaging of spinal infections

The diagnosis of spinal infection, with or without implants, has been a challenge for physicians for many years. Spinal infections are now being recognised more frequently, owing to aging of the population and the increasing use of spinal-fusion surgery. The diagnosis in many cases is delayed, and this may result in permanent neurological damage or even death. Laboratory evidence of infection is variable. Conventional radiography and radionuclide bone imaging lack both sensitivity and specificity. Neither in vitro labelled leucocyte scintigraphy nor 99mTc-anti-granulocyte antibody scintigraphy is especially useful, because of the frequency with which spinal infection presents as a non-specific photopenic area on these tests. Sequential bone/gallium imaging and 67Ga-SPECT are currently the radionuclide procedures of choice for spinal osteomyelitis, but these tests lack specificity, suffer from poor spatial resolution and require several days to complete. [18F]Fluoro-2-deoxy-D-glucose (FDG) PET is a promising technique for diagnosing spinal infection, and has several potential advantages over conventional radionuclide tests. The study is sensitive and is completed in a single session, and image quality is superior to that obtained with single-photon emitting tracers. The specificity of FDG-PET may also be superior to that of conventional tracers because degenerative bone disease and fractures usually do not produce intense FDG uptake; moreover, spinal implants do not affect FDG imaging. However, FDG-PET images have to be read with caution in patients with instrumented spinal-fusion surgery since non-specific accumulation of FDG around the fusion material is not uncommon. In the future, PET-CT will likely provide more precise localisation of abnormalities. FDG-PET may prove to be useful for monitoring response to treatment in patients with spinal osteomyelitis. Other tracers for diagnosing spinal osteomyelitis are also under investigation, including radiolabelled antibiotics, such as 99mTc-ciprofloxacin, and radiolabelled streptavidin-biotin complex. Antimicrobial peptides display preferential binding to microorganisms over human cells and perhaps new radiopharmaceuticals will be recruited from the array of human antimicrobial peptides/proteins. In experiments with Tc-ubiquicidin-derived peptides, radioactivity at the site of infection correlated well with the number of viable bacteria present. Finally, radiolabelled antifungal tracers could potentially distinguish fungal from bacterial infections.

Pitfalls in Integrated CT-PET of the Thorax: Implications in Oncologic Imaging

Integrated computed tomography-positron emission tomography (CT-PET) scanners improve localization of regions of increased [18F]-fluoro-2-deoxy-D-glucose (FDG) uptake and staging accuracy by allowing the near-simultaneous acquisition of coregistered, spatially matched functional and morphologic data in the same examination. However, many benign lesions can accumulate FDG and be potential pitfalls in interpretation. With the increased use of CT-PET in oncologic imaging, misinterpretation of these potential pitfalls can have significant clinical ramifications and alter staging and management. In this article, we review the physiologic uptake of FDG, normal variants, and potential pitfalls in the integrated CT-PET imaging of the thorax and their implications in oncologic imaging.

Development of real-time bioradiographic system for functional and metabolic imaging in living brain tissue

We have developed a novel imaging system “real-time bioradiography”, which is able to estimate the dynamic changes of physiological function and metabolism in living tissues using positron emitter-labeled tracers and chemiluminescence probes. The apparatus is comprised of a photon-counting camera, image-controller, culturing chamber, reflexible solid scintillator and temperature-controlled imaging chamber. The image distribution of radioactivity and chemiluminescence was acquirable with the reflexible solid scintillator and without, respectively. The reflexible solid scintillator is effective to exclude the affect of intra-objective different light reflectivity on radiation detection and to improve the efficiency of radiation detection. To test and to demonstrate the efficacy of this system, we examined the glucose metabolism and superoxide formation during hypoxia-reoxygenation in living brain tissues using 2-[ 18F]fluoro-2-deoxy- d-glucose (FDG) and Lucigenin, respectively. FDG uptake and chemiluminescence images were obtained at time frames of every 15 min. Glucose metabolism was enhanced during the hypoxic treatment, but the superoxide formation was enhanced during reoxygenation. The enhanced glucose metabolism during hypoxia might cause the increase in superoxide formation during reoxygenation. Thus, this new method would open up possibilities to approach simultaneous biological monitoring of a variety of biochemical events with various combinations of positron emitter-labeled tracers and chemiluminescence probes in living tissues.

F-18 FDG PET Superscan

A 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) scan of a patient with diffuse bony metastases from a poorly differentiated renal adenocarcinoma demonstrated multiple bony metastatic lesions with brisk, enhanced uptake of FDG but only faint visualizations of the brain, liver, renal cortex, and soft tissue. These FDG PET images are similar to the superscan seen on Tc-99m-methylene diphosphonate bone scintigraphy.

FDG gamma camera PET equipped with one inch crystal and XCT

Metabolic imaging with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) is actually considered as the best method to detect and quantitatively assess myocardial tissue viability. The aim of this study was to investigate the accuracy of FDG gamma camera positron emission tomography (GCPET) imaging equipped with one inch NaI crystals in comparison to FDG dedicated PET (dPET) imaging as a "gold standard" in phantom and clinical studies. Nineteen patients with coronary artery disease (CAD) underwent both imaging modalities. Phantom and clinical GCPET imaging were performed with a dual-headed, coincidence based gamma camera equipped with 1 inch thick NaI crystals and an x-ray tube (XCT) for attenuation correction (AC), as well as with a dedicated PET scanner with AC. (99m)Tc tetrofosmin single-photon emission tomography (SPET) studies were performed for assessment of myocardial perfusion, with AC. Phantom studies showed a significant relation in segmental activity between FDG imaging with AC using GCPET and dPET (r = 0.91, p < 0.001). In clinical studies with AC correlation coefficients of mean segmental FDG uptake and regional defect size were r = 0.87 (p < 0.0001) and r = 0.83 (p < 0.0001), respectively. In regional analysis close agreement was even found in the most attenuated regions of the heart if AC was used in GCPET imaging. The overall agreement for detection of viable myocardium was 81% between FDG-dPET (AC) and FDG-GCPET (AC) and 74% between FDG-dPET (AC) and FDG-GCPET (NC). This study suggests that the assessment of myocardial metabolism by means of FDG is feasible with a coincidence based gamma camera equipped with 1 inch thick NaI crystals if AC is performed. The results reveal a close concordance and agreement between FDG-dPET (AC) and FDG-GCPET (AC) as compared to FDG-GCPET (NC).

PTLD Visualization by FDG-PET: Improved Detection of Extranodal Localizations and Response Monitoring.

Posttransplant lymphoproliferative disease (PTLD) is a serious complication that may arise after solid organ transplantation. PTLD may involve nodal as well as extranodal sites, with frequent involvement of the allograft and digestive tract. Extranodal localizations of PTLD may not always be visualized with routine conventional diagnostic methods such as computer tomography (CT) or magnetic resonance imaging (MRI). Our aim was to evaluate the value of 2-[18F] fluoro-2-deoxy-D-glucose (FDG)-PET in the staging and treatment evaluation of histologically confirmed PTLD (patient #3 confirmed by ascites cytology) in 10 kidney transplant recipients transplanted between January 2000 and June 2004. At time of PTLD diagnosis patients were fully staged by standard conventional diagnostic methods according to lymphoma protocols, including at least whole body CT scanning and bone marrow biopsy. In addition, whole body-mode PET studies were performed. All patients had their scans prior to therapy. In addition, four had repeated PET-scans during and after therapy. To compare CT with FDG-PET, all scans were re-evaluated (blinded) by a radiologist and an expert in nuclear medicine, respectively. All PET-scans at initial diagnosis could readily be interpreted and showed high FDG uptake in the primary sites of histological confirmed PTLD. This was true for monomorphic as well as polymorphic PTLD. The large majority of other sites of involvement as detected by conventional diagnostic methods at diagnosis were also PET positive. However, additional extranodal sites were detected by FDG-PET not readily visualized by CT scanning (table 1). After treatment with Rituximab, a decline or disappearance of FDG-uptake coincided with clinical response as detected by conventional diagnostic methods. These findings suggest that FDG-PET is suitable in visualization of (different histological subtypes of) PTLD and useful for both staging and response to treatment evaluation. The ability of FDG-PET to visualize extranodal localizations of PTLD, often present but not readily detectable by routine conventional diagnostic methods, is of additional value.Sites of PTLD involvement at diagnosis: CT and PET comparedPatientSite of BiopsyAnn Arbor StageDiagnosis*PETCT1liverIVjugular, supraclavicular, axillar, mediastinum, lung hili, liver , spleen, para-aortal, paracaval, bone marrowspleen, para-aortal, para-caval2ascitesIVno abnormal fociNo abnormalities3colonIVmultiple foci abdomen ventralNo abnormalities4cerebrumIEcerebrumcerebrum**5pancreasIEpancreaspancreas6lymph node jugularIVlymph node jugular , small pelvic, rectum, surrounding allograftsmall pelvic, right groin7lymph node axillarIVjugular, axillar, liver, rectum, bone marrowjugular, axillar, mediastinum, para-caval ,8stomachIVsupraclavicular, infraclavicular, mediastinum, multiple foci retroperitoneal, stomach, multiple foci abdomensupraclavicular, infraclavicular, mediastinum, para-caval, para-aortal, stomach, central abdomen9cerebrumIEcerebrumcerebrum**10skin left legIEskin left legno other sites involved*Disconcordant lesions are bolded, **confirmed by MRI

Adjusted Scaling of FDG Positron Emission Tomography Images for Statistical Evaluation in Patients With Suspected Alzheimer's Disease

Statistical parametric mapping (SPM) gained increasing acceptance for the voxel-based statistical evaluation of brain positron emission tomography (PET) with the glucose analog 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) in patients with suspected Alzheimer's disease (AD). To increase the sensitivity for detection of local changes, individual differences of total brain FDG uptake are usually compensated for by proportional scaling. However, in cases of extensive hypometabolic areas, proportional scaling overestimates scaled uptake. This may cause significant underestimation of the extent of hypometabolic areas by the statistical test. To detect this problem, the authors tested for hypermetabolism. In patients with no visual evidence of true focal hypermetabolism, significant clusters of hypermetabolism in the presence of extended hypometabolism were interpreted as false-positive findings, indicating relevant overestimation of scaled uptake. In this case, scaled uptake was reduced step by step until there were no more significant clusters of hypermetabolism. In 22 consecutive patients with suspected AD, proportional scaling resulted in relevant overestimation of scaled uptake in 9 patients. Scaled uptake had to be reduced by 11.1% +/- 5.3% in these cases to eliminate the artifacts. Adjusted scaling resulted in extension of existing and appearance of new clusters of hypometabolism. Total volume of the additional voxels with significant hypometabolism depended linearly on the extent of the additional scaling and was 202 +/- 118 mL on average. Adjusted scaling helps to identify characteristic metabolic patterns in patients with suspected AD. It is expected to increase specificity of FDGPET in this group of patients.

Adjusted Scaling of FDG Positron Emission Tomography Images for Statistical Evaluation in Patients With Suspected Alzheimer's Disease

ABSTRACTBackground and Purpose. Statistical parametric mapping (SPM) gained increasing acceptance for the voxel‐based statistical evaluation of brain positron emission tomography (PET) with the glucose analog 2‐[18F]‐fluoro‐2‐deoxy‐d‐glucose (FDG) in patients with suspected Alzheimer's disease (AD). To increase the sensitivity for detection of local changes, individual differences of total brain FDG uptake are usually compensated for by proportional scaling. However, in cases of extensive hypometabolic areas, proportional scaling overestimates scaled uptake. This may cause significant underestimation of the extent of hypometabolic areas by the statistical test. Methods. To detect this problem, the authors tested for hyper metabolism. In patients with no visual evidence of true focal hypermetabolism, significant clusters of hypermetabolism in the presence of extended hypometabolism were interpreted as false‐positive findings, indicating relevant overestimation of scaled uptake. In this case, scaled uptake was reduced step by step until there were no more significant clusters of hypermetabolism. Results. In 22 consecutive patients with suspected AD, proportional scaling resulted in relevant overestimation of scaled uptake in 9 patients. Scaled uptake had to be reduced by 11.1%± 5.3% in these cases to eliminate the artifacts. Adjusted scaling resulted in extension of existing and appearance of new clusters of hypometabolism. Total volume of the additional voxels with significant hypometabolism depended linearly on the extent of the additional scaling and was 202 ± 118 mL on average. Conclusions. Adjusted scaling helps to identify characteristic metabolic patterns in patients with suspected AD. It is expected to increase specificity of FDGPET in this group of patients.

Combined PET-CT in the Head and Neck

Positron emission tomography (PET) with 2-[fluorine-18] fluoro-2-deoxy-D-glucose (FDG) is effective for monitoring head and neck cancer. However, lack of anatomic landmarks, variable physiologic FDG uptake, and asymmetric FDG distribution in the neck can confound image interpretation. This is particularly true in the treated neck, where distortion of normal tissue planes makes detection of early disease recurrence difficult with conventional computed tomography (CT) and magnetic resonance imaging. Combined PET-CT helps prevent the misinterpretation of FDG PET findings in patients with head and neck cancer. Superior localization of FDG uptake with this technique can improve diagnostic accuracy and help avoid interpretative pitfalls. In the future, development of tumor-specific ligands will enhance the usefulness of PET-CT in the detection of initial tumors and tumor recurrence, in the evaluation of tumors with low FDG avidity, and in treatment targeting. Furthermore, improved scanner resolution will help address the limitations of PET-CT with respect to small lesions and may make this modality more valuable in initial tumor staging.

Combined PET-CT in the Head and Neck

Positron emission tomography (PET) with 2-[fluorine-18] fluoro-2-deoxy-D-glucose (FDG) has been effective for the diagnosis, staging, and restaging of malignancies of the head and neck region. However, lack of anatomic landmarks, variable physiologic uptake, and asymmetric FDG distribution in several altered physiologic states can confound image interpretation. In addition, many benign causes and several artifacts can simulate physiologic or pathologic FDG uptake in the head and neck. Combined PET-computed tomography (CT) is a unique imaging modality that permits anatomic and functional imaging on a single scanner with nearly perfect coregistration. Combined PET-CT provides information that cannot be obtained with PET or CT alone. In particular, PET-CT facilitates the interpretation of FDG uptake in the head and neck, an area that is characterized by dense and complex anatomic structures. An atlas of FDG uptake in this anatomic region was compiled on the basis of combined PET-CT findings in 11,000 patients. In general, patterns of FDG uptake were variable and often reflected patient activity during or immediately preceding the uptake phase. With the growing interest in PET-CT, interpreting radiologists and nuclear medicine physicians must be familiar with the patterns of FDG uptake in the head and neck to avoid misinterpretation or mis-diagnosis.

Activation of thymidine salvage pathway measured with FLT PET, as a potential indicator of response to 5FU in colorectal cancer

3572 Background: The commonly used positron emission tomography (PET) tracer is [18F]-Fluoro-2-deoxy-D-glucose (FDG). [18F]-3-fluoro-3-deoxy-L-thymidine (FLT) is a novel tracer, with cellular uptake mechanisms linked to the pyrimidine salvage enzyme, thymidine kinase-1 (TK-1). The colorectal cancer chemotherapeutic agent, 5-Fluorouracil (5FU), inhibits de novo pyrimidine synthesis. Therefore, we investigated changes in FLT and FDG uptake after 5FU treatment, to determine their potential in detecting early evidence of response to 5FU in vitro. Methods: Human colorectal cancer cell cultures (SW480, SW620) were treated with 5FU (50μg/ml, 2h). Cells were washed, incubated with FLT or [18F]-Fluoro-2-deoxy-D-glucose (FDG) for comparison (100kBq, 90 min). Cells were subsequently harvested and uptake was determined using a gamma counter. TK-1 expression was detected by Western blotting. Changes in S-phase fraction (SPF) of treated cell were examined by flow cytometry. Results: Cytotoxic dose of 5FU chosen showed minimal cell killing immediately after treatment (0–10% (p=NS). However, 50% cell killing was achieved at 24 hours. A mean 2.96 fold increase (2.82 ± 0.2, SW480; 3.10± 0.3 SW620) in total FLT uptake (per 10 5 cells) was observed in treated cells vs controls (p<0.01). However, no difference was observed in FDG uptake. The increase in FLT uptake post 5FU treatment correlated with increased TK-1 expression in both cell lines. No significant change in the SPF of 5FU treated cells was observed. Conclusions: An early biological response to 5FU treatment was measured with FLT and not FDG. This effect correlated with an increased expression of thymidine salvage enzyme TK-1, before changes in the cell cycle were observed. FLT PET may potentially be used as an indicator of response to 5FU based chemotherapeutic agents before changes in morphology become apparent. No significant financial relationships to disclose.

Diagnostic accuracy of FDG PET imaging for the detection of recurrent or metastatic gynecologic cancer

This study evaluated the diagnostic role and accuracy of positron emission tomography (PET) using 2-[F-18]fluoro-2-deoxy-D-glucose (FDG) for the detection of tumor foci in patients with suspected recurrent or metastatic lesions of gynecologic cancers. FDG PET imaging was performed on 51 patients with a previous history of gynecologic cancer who were referred for a clinical suspicion of recurrent disease. PET acquisition was started 50-60 min after the intravenous injection of 5-6 MBq/kg FDG in all patients. The PET images were interpreted visually, and tracer uptake was quantitated as the standardized uptake value adjusted to body weight (SUV) in the lesions showing FDG uptake. The accuracy of the PET results was assessed by a consensual verdict based on histology, cytology, other imaging and clinical follow-up. FDG PET correctly diagnosed 33 of 36 patients with recurrent disease and 12 of 15 patients without recurrence. On patient-based analysis, the sensitivity, specificity and accuracy of FDG PET were 91.7%, 80.0% and 88.2%, respectively, depending on the selected scheme for visual scoring of the lesions. The area index in receiver-operating characteristic analysis was 0.95 for patient detection. Malignant lesions accumulated significantly more FDG than the benign ones (the mean SUVs were 3.7 +/- 1.9 and 1.6 +/- 1.1, respectively, p = 0.004). The sensitivity and specificity in correct identification of tumor recurrence or metastases using a threshold SUV 1.9 were 88.8% and 66.7% in contrast to the visual analysis (sensitivity 96.4%, specificity 50%) on a lesion-based analysis. The partial volume effect of SUV in a few small lesions and the presence of bone lesions in which FDG uptake was relatively low might be the reason for the lower sensitivity in SUV analysis. FDG PET was valuable when CT/MRI was negative or inconclusive, and in patients with elevated tumor marker levels as well as with normal tumor marker levels when recurrence was suspected clinically. However, PET failed to visualize some small metastatic lesions in lung and bone, and showed falsely high FDG uptake in some benign lesions. The results indicated that FDG PET is a reliable and accurate diagnostic method for detecting recurrent or metastatic gynecologic cancer particularly lymph node metastases. Although the sensitivity of PET for detecting small metastases was relatively limited, the overall sensitivity of FDG PET was significantly higher than morphologic imaging.

18F]3′-deoxy-3′-fluorothymidine PET for the diagnosis and grading of brain tumors

The aim of this study was to evaluate the feasibility of using [(18)F] 3'-deoxy-3'-fluorothymidine (FLT) positron emission tomography (PET) for the diagnosis and grading of brain tumors. The patient population comprised 26 patients (15 males, 11 females) with brain tumors (n=18) or nontumorous lesions (n=8). 2-[(18)F]fluoro-2-deoxy-D: -glucose (FDG) and FLT PET images were obtained using a dedicated PET scanner 1 h after the injection of 370 MBq of FDG or FLT. Uptake of FDG and FLT by the lesions was visually and semiquantitatively assessed in comparison with normal brain tissue. Of 26 brain lesions, four showed increased FDG uptake compared with normal gray matter (grade 5). These four lesions showed intensely increased FLT uptake and were all high-grade tumors. Twenty-two lesions with similar (grade 4) or decreased (grades 1-3) FDG uptake compared with normal gray matter showed variable pathology. Among the 18 brain tumors, FLT PET showed increased uptake in all 12 high-grade tumors but FDG uptake was variable. In 22 brain lesions with similar or decreased uptake compared with normal gray matter on FDG PET, the sensitivity and specificity of FLT PET for the diagnosis of brain tumor were 79% (11/14) and 63% (5/8), respectively. The uptake ratios of 14 brain tumors on FLT PET were significantly higher than the lesion to gray matter ratios (p=0.012) and lesion to white matter ratios (p=0.036) of FDG uptake and differed significantly between high (5.1+/-2.6) and low (2.1+/-1.1) grade tumors (p=0.029). In nine gliomas, FLT uptake was significantly correlated with the Ki-67 proliferation index (rho=0.817, p=0.007). These findings indicate that FLT PET is useful for evaluating tumor grade and cellular proliferation in brain tumors. It displayed high sensitivity and good contrast in evaluating brain lesions that showed similar or decreased uptake compared with normal gray matter on FDG PET. FLT PET, however, did not appear to be sufficiently useful for differentiating tumors from nontumorous lesions.

Positron-Emission Tomography Imaging of Early Events after Transplantation of Islets of Langerhans

The aim of our study was to assess cell trafficking and early events after intraportal islet transplantation. Sprague-Dawley rat islets were incubated for various times, with various concentrations of 2-[F]fluoro-2deoxy-D-glucose (FDG), and in presence of various glucose concentrations. FDG-labeled syngeneic islets or FDG alone were injected in rats. Radioactivity was measured in the liver and in various organs by positron-emission tomography for 6 hours. FDG uptake increased with incubation time or FDG concentration and decreased in presence of glucose. In vivo, all islets implanted in the liver, with an uptake 4.4 times higher than controls (44.2% vs. 10.1%, P=0.02). Radioactivity in the liver decreased at the same rate after injection of labeled-islets and FDG alone. Ex vivo labeling of islets and imaging of posttransplant early events were feasible. Islets engrafted exclusively in the liver. No islet loss could be demonstrated 6 hours after transplantation.