Evaluation of thoracic tumors with 18F-fluorothymidine and 18F-fluorodeoxyglucose-positron emission tomography.

STUDY OBJECTIVES: 18F-fluorodeoxyglucose (FDG) is the most widely used positron emission tomography (PET) imaging probe used for the diagnosis, staging, restaging, and monitoring therapy response of cancer. However, its specificity is less than ideal. A new molecular imaging probe (18F-deoxyfluorothymidine [FLT]) has been developed that might afford more specific tumor imaging. The aims of this study were as follows: (1) to compare the use of FDG-PET and FLT-PET for tumor staging, (2) to compare the degree of FDG and FLT uptake in lung lesions, and (3) to determine the correlation between PET uptake intensity and tumor cell proliferation. DESIGN: FDG-PET and FLT-PET scans were performed in 11 patients with solitary pulmonary nodules and another 11 patients with known non-small cell lung cancer (NSCLC). Tracer uptake was assessed quantitatively by standardized uptake values (SUVs). Histologic evaluation of tissue samples obtained from biopsy specimens or surgical resections served as the "gold standard." Tumor cell proliferation was assessed by Ki-67 staining. RESULTS: Pathology verification was available from 99 tissue samples in the 22 patients (29 pulmonary lesions, 66 lymph node stations, and 4 extrapulmonary lesions). Thirty-three samples (33.3%) were positive for tumor tissue (22 pulmonary, 9 lymph node stations, and 2 extrapulmonary). FDG-PET findings were false-positive in three pulmonary lesions, while FLT-PET findings were false-positive in one lesion. There were two false-negative findings by FDG-PET and six false-negative findings by FLT-PET. FDG uptake of the malignant lesions was significantly higher than FLT (maximum SUV, 3.1 +/- 2.6 vs 1.6 +/- 1.2 [mean +/- SD]; p < 0.05). A significant correlation was observed between FLT uptake of pulmonary lesions and Ki-67 labeling index (r = 0.60, p = 0.02) but not for FDG uptake (r = 0.27, p = not significant). CONCLUSIONS: Compared to FDG-PET, detection of primary and metastatic NSCLC by FLT-PET is limited by the relatively low FLT uptake of the tumor tissue. Thus, FLT-PET is unlikely to provide more accurate staging information or better characterization of pulmonary nodules than FDG-PET. Nevertheless, the correlation between FLT uptake and cellular proliferation suggests that future studies should evaluate the use of FLT-PET for monitoring treatment with cytostatic anticancer drugs.

Cardiac pacemakers and central venous lines can induce focal artifacts on CT-corrected PET images.

UNLABELLED: PET/CT imaging can be associated with focal artifactual (18)F-FDG uptake introduced by metallic implants or contrast agents. It is unknown whether cardiac pacemakers or permanent central venous catheters can also result in such artifacts. METHODS: Twenty-seven patients with permanent central venous lines (13 men and 14 women; mean age +/- SD, 53.8 +/- 16.2 y) and 9 patients with pacemakers (7 men and 2 women; mean age +/- SD, 74.8 +/- 5.1 y) who were referred for a variety of oncologic indications were studied with lutetium-oxyorthosilicate-based dual-slice PET/CT after injection of 7.77 MBq/kg of (18)F-FDG. CT-corrected and -uncorrected PET images were reviewed, and (18)F-FDG uptake was graded as absent, mild, moderate, or intense. RESULTS: CT-corrected PET images revealed focally increased uptake of moderate intensity in all patients with cardiac pacemakers and focally increased uptake of mild intensity in 8 of 27 patients (29.6%) with central venous lines. CONCLUSION: Cardiac pacemakers and reservoirs of central venous lines can induce artifactual (18)F-FDG on CT-corrected PET images. Thus, in patients with permanent central lines or pacemakers, both corrected and uncorrected PET images need to be reviewed to avoid false-positive PET findings.

The impact of PET on the management of lung cancer: the referring physician's perspective.

UNLABELLED: (18)F-FDG PET is a molecular whole-body imaging modality that is increasingly being used for diagnosing, staging, and restaging cancer. The objective of this study was to determine referring physicians' perspectives on the impact of (18)F-FDG PET on staging and management of lung cancer. METHODS: A questionnaire was sent to the 292 referring physicians of 744 consecutive patients with known or suspected lung cancer who were evaluated with PET. Questionnaires on 274 patients were returned (response rate, 37%). Management changes were categorized as intermodality (e.g., surgery to medical, surgery to radiation, and medical to no treatment) or intramodality (e.g., altered medical, surgical, or radiotherapy approach). RESULTS: The primary reasons for PET referral were staging of lung cancer in 61% of patients, diagnosis in 20%, and monitoring of therapy or the course of disease in 6%. Physicians reported that PET caused them to change their decision on clinical stage in 44% of all patients: The disease was upstaged in 29% and downstaged in 15%. PET resulted in intermodality management changes in 39% of patients, whereas 15% had an intramodality change. CONCLUSION: This survey-based study of referring physicians suggests that PET has a major impact on staging and management of lung cancer.

Conventional imaging and 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography for predicting the clinical outcome of patients with previously treated Hodgkin's disease.

PURPOSE: The aim of this study was to determine the ability of 2-deoxy-2-[(18)F]fluoro-d-glucose positron emission tomography (FDG-PET) to predict the clinical outcome of previously treated patients with Hodgkin's Disease (HD). PATIENTS AND METHODS: Thirty-two patients were studied with PET within a median interval of 5.2 months after treatment. Conventional imaging (CI) performed within two months before PET included 2.9+/-1.2 imaging tests/patient. To determine the independent ability of FDG-PET to predict the clinical outcome, PET images were reread without knowledge of CI and clinical history. Study end points were disease-free survival, or clinical evidence of disease or death. PET and CI stages were also compared for each patient. RESULTS: Using the clinical outcome as gold standard after a median follow-up of 14 months, 21 of 32 patients (65%) were considered disease-free while 11 of 32 patients (35%) had evidence for disease or had died. The predictive accuracy of PET was 91% vs. 66% for conventional imaging (P<0.05). The positive predictive value (PPV) was also significantly higher for PET (79% vs. 50%, P<0.05), while its negative predictive value (NPV) tended to be higher than that of CI (100% vs. 86%, P=0.08). Kaplan-Meier analysis for disease-free survival showed a significant difference between PET-negative and -positive results. No such difference was observed between CI-positive and -negative results (P=0.35). CONCLUSION: Whole-body FDG-PET imaging modified the clinical stage in 28% of patients. Moreover, FDG-PET predicted patient outcome with a higher predictive accuracy than CI. This superior prognostic accuracy was achieved with a single FDG-PET study vs. 2.9+/-1.2 CI procedures/patient.

Indirect monitoring of endogenous gene expression by positron emission tomography (PET) imaging of reporter gene expression in transgenic mice.

PURPOSE: Repetitive imaging with microPET of endogenous albumin gene expression by using transgenic mice in which the Herpes Simplex Virus Type 1 thymidine kinase (HSV1-tk) reporter gene is driven by the albumin promoter (AL-HSV1-tk). METHODS: Transgenic mice were imaged repeatedly on a microPET scanner with approximately 200 microCi of 9-[4-[18F]fluoro-3-(hydroxymethyl)butyl]guanine (FHBG) (a substrate for HSV1-TK enzyme). Four transgenic mice were monitored for body weight, serum albumin, and imaged at the end of each of three dietary phases (17%, 0%, and 25% protein diet). Each phase last 14-21 days. The 0% protein diet has been reported previously to reduce albumin gene expression in rats. Twenty non-transgenic mice of the same strain followed a similar feeding schedule and were monitored for serum albumin, body weight, and sacrificed at various time points for determination of their GAPDH normalized albumin mRNA levels. RESULTS: Transgenic mice showed a relatively high FHBG signal from the liver region as expected. Variation of the mean FHBG signal in two mice with a fixed 17% protein diet over a four-month period was <19% s.d. The mean +/- s.e. FHBG liver standardized uptake value (SUV) in four transgenics went from 4.49 +/- 0.32 to 2.17 +/- 0.52 to 6.21 +/- 0.72 as the mice went through the three diets of 17%, 0%, and 25% sequentially. Non-transgenic mice showed GAPDH normalized albumin mRNA that went from 37.68 +/- 6.04 to 26.41 +/- 4.29 to 52.42 +/- 4.09. The FHBG SUV from transgenics was well correlated with GAPDH normalized albumin mRNA from non-transgenics (r(2) = 0.97) supporting that endogenous gene expression of albumin can be indirectly imaged with FHBG. CONCLUSION: Measuring correlated changes in albumin expression in wild type mice and HSV1-TK expression by microPET in transgenic mice in which the reporter gene is driven by the albumin promoter demonstrates that the HSV1-tk gene can be used to monitor, in living animals, modulated expression of transgenes.

FDG-PET imaging in lung cancer: how sensitive is it for bronchioloalveolar carcinoma?

While characterization of lung lesions and staging of lung cancer with fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is an established clinical procedure, a lower diagnostic accuracy of FDG-PET for diagnosis and staging of so-called bronchioloalveolar carcinoma (BAC) has been reported. Therefore, the accuracy of PET for diagnosing and staging of BAC was investigated. We studied 41 patients eventually found to have adenocarcinoma with a bronchioloalveolar growth pattern who were referred for characterization or staging of lung lesions with whole-body FDG-PET between January 1998 and March 2001: there were 11 males (27%) and 30 females (73%), with a mean age of 66.0+/-10.9 (range =44-84 years). Patients were imaged using ECAT EXACT or HR+ systems. All patients had non-attenuation-corrected scans, while transmission data for attenuation correction were also available for 12 patients (29%). PET correctly identified BAC in 41 of the 46 (89%) lesions and 39 of the 41 patients (95%). By pathology, 25 patients (61%) were found to have unifocal or nodular lesions; this pattern was correctly identified by PET in 20 patients (80%) and by CT in 18 (72%). PET correctly identified 7 (44%) of 16 patients (39%) who had multicentric or diffuse BAC, and CT identified 11 (69%). Of the 35 patients whose lymph node status was verified pathologically, PET was correct in 27 (77%) and CT in 24 (69%). PET missed 67% of the rare tumors that had a pure BAC pattern with no invasive component. It is concluded that the diagnostic performance of whole-body FDG-PET is similar in most patients with lesions with a BAC pattern and in other non-small cell lung cancer types. PET is less accurate in patients with rare BAC tumors that have no invasive component.