18F-FDG uptake as a biologic prognostic factor for recurrence in patients with surgically resected non-small cell lung cancer.

Among patients with resected non-small cell lung cancer (NSCLC), approximately 50% present with a recurrent tumor. The clinical or pathologic TNM staging does not always provide a satisfactory explanation for differences in relapse and survival. Thus, it is of major importance to be able to predict these relapses and to prevent them with an active chemotherapy or radiotherapy program (or both). 18F-FDG uptake on PET could be of prognostic significance in patients with resected NSCLC. The goal of this study was to determine whether the level of metabolic activity observed with 18F-FDG uptake correlates with the probability of postoperative recurrence in patients with NSCLC. METHODS: Fifty-seven patients with NSCLC were examined with 18F-FDG PET. For semiquantitative analysis, standardized uptake values (SUVs) were calculated. Patients were classified into high-SUV (> 5.0) and low-SUV (< or = 5.0) groups. All patients underwent thoracotomy within 4 wk after the 18F-FDG PET study. Tumor 18F-FDG uptake (SUV), pathologic stage, and lesion size were analyzed for their possible association with disease-free survival. RESULTS: Forty-six patients had pathologic stage I NSCLC and 11 had pathologic stage II or stage III NSCLC. In a univariate analysis, patients with an SUV of < or = 5 had a much better disease-free survival than did patients with an SUV of > 5 (P < 0.0001). In patients with pathologic stage I and stage IA NSCLC, the SUV was also correlated with disease-free survival (P < 0.0001 and P = 0.0012, respectively). Patients with pathologic stage I disease had an expected 5-y disease-free survival rate of 88% if the SUV was < or = 5 and a survival rate of < or = 17% if the SUV was > 5. A multivariate Cox analysis identified the SUV as the most significant independent factor for disease-free survival. CONCLUSION: We conclude that the 18F-FDG uptake in primary NSCLC determined by PET has a significant independent postoperative prognostic value for recurrence, especially in patients with pathologic stage I NSCLC. 18F-FDG uptake was superior to pathologic stage in predicting relapse of patients with NSCLC.     

Comparison of 18F-FLT PET and 18F-FDG PET in esophageal cancer.

18F-FDG PET has gained acceptance for staging of esophageal cancer. However, FDG is not tumor specific and false-positive results may occur by accumulation of FDG in benign tissue. The tracer 18F-fluoro-3'-deoxy-3'-L-fluorothymidine (18F-FLT) might not have these drawbacks. The aim of this study was to investigate the feasibility of 18F-FLT PET for the detection and staging of esophageal cancer and to compare 18F-FLT PET with 18F-FDG PET. Furthermore, the correlation between 18F-FLT and 18F-FDG uptake and proliferation of the tumor was investigated. METHODS: Ten patients with biopsy-proven cancer of the esophagus or gastroesophageal junction were staged with CT, endoscopic ultrasonography, and ultrasound of the neck. In addition, all patients underwent a whole-body 18F-FLT PET and 18F-FDG PET. Standardized uptake values were compared with proliferation expressed by Ki-67 positivity. RESULTS: 18F-FDG PET was able to detect all esophageal cancers, whereas 18F-FLT PET visualized the tumor in 8 of 10 patients. Both 18F-FDG PET and 18F-FLT PET detected lymph node metastases in 2 of 8 patients. 18F-FDG PET detected 1 cervical lymph node that was missed on 18F-FLT PET, whereas 18F-FDG PET showed uptake in benign lesions in 2 patients. The uptake of 18F-FDG (median standardized uptake value [SUV(mean)], 6.0) was significantly higher than 18F-FLT (median SUV(mean), 3.4). Neither 18F-FDG maximum SUV (SUV(max)) nor 18F-FLT SUV(max) correlated with Ki-67 expression in the linear regression analysis. CONCLUSION: In this study, uptake of 18F-FDG in esophageal cancer is significantly higher compared with 18F-FLT uptake. 18F-FLT scans show more false-negative findings and fewer false-positive findings than do 18F-FDG scans. Uptake of 18F-FDG or 18F-FLT did not correlate with proliferation.     

18F-FDG uptake on PET helps predict outcome and response after treatment in unresectable thymic epithelial tumors

Background

Positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (¹⁸F-FDG) has been studied in thymic epithelial tumors. We evaluated the usefulness of ¹⁸F-FDG PET for monitoring after treatment in unresectable thymic epithelial tumors.

Method

Twelve patients with unresectable/metastatic thymic epithelial tumors underwent PET study with ¹⁸F-FDG before and after chemotherapy or radiotherapy. Response and survival were analyzed according to the ratio of the peak standardized uptake value (SUV) of the tumor to the mean SUV of the mediastinum (T/M ratio).

Results

Partial response (PR) evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) was noted in 4 (33%) of 12 patients, and partial metabolic response (PMR) was observed in 6 (50%) of 12 patients. PR was observed in 4 of 6 patients with PMR. In 6 patients with any response, the T/M ratio at post-treatment was significantly lower than at baseline (p = 0.0017). In 6 patients with stable disease (SD), stable metabolic disease (SMD) was observed in 5 by use of ¹⁸F-FDG PET. No statistically significant difference of ¹⁸F-FDG uptake between at baseline and post-therapy was observed in 6 patients with SD (p = 0.4157) and SMD (p = 0.8419). Although the overall survival after treatment showed no statistically significant difference between PMR and SMD or progressive metabolic disease in the whole group of patients including thymoma, a statistically significant difference in the overall survival was observed between 5 patients with PMR and 5 patients with non-PMR (p = 0.0280).

Conclusion

Our preliminary study suggests that ¹⁸F-FDG PET is useful for monitoring response and outcome after treatment in unresectable thymic epithelial tumors.     

Bone marrow hypermetabolism on 18F-FDG PET as a survival prognostic factor in non-small cell lung cancer.

PET is now widely used in the diagnosis and staging of lung cancer with (18)F-FDG. The purpose of the study was to evaluate the prognostic value of diffuse bone marrow hypermetabolism along with other PET prognostic factors with respect to survival and compare them with other established prognostic factors in a large cohort of patients. METHODS: Of 255 patients referred for evaluation of a suspicious lung lesion by PET over an 8-mo period (May 1999 to January 2000), the outcome of 120 patients with a final diagnosis of primary non-small cell lung cancer was analyzed retrospectively after excluding subjects with benign, metastatic, or recurrent lesions, using the available follow-up information and a provincial mortality database. Kaplan-Meier survival curves were compared using the mean and the maximal tumor standardized uptake value (SUV), bone marrow SUV, PET stage, various laboratory parameters, sex, age, conventional imaging stage, and pathologic stage. A stepwise Cox proportional hazard model was built using the significant variables on univariate analysis. RESULTS: The primary tumor SUV (>10), bone marrow uptake of (18)F-FDG, (18)F-FDG PET stage, pathologic stage, hypercalcemia, lactate dehydrogenase, hemoglobin, albumin, thrombocytopenia, thrombocytosis, and leukocytosis were predictors of mortality on univariate analysis. On multivariate analysis, bone marrow hypermetabolism, (18)F-FDG PET nodal stage, and some hematologic parameters (hemoglobin, platelets, white blood cell counts) remained significant independent predictors of mortality. CONCLUSION: Bone marrow hypermetabolism and the PET nodal stage were strong independent predictors of mortality in patients with lung cancer. The primary tumor SUV, though predictive on univariate analysis, was not an independent predictor of mortality in our model.     

18F-FDG PET is an early predictor of pathologic tumor response to preoperative radiochemotherapy in locally advanced rectal cancer.

18F-FDG PET is a useful tool for assessing the effects of chemo- or radiotherapy. The aim of this study was to correlate the change in tumor 18F-FDG standardized uptake value (SUV) during and after preoperative radiochemotherapy, with the pathologic response achieved in locally advanced rectal cancer (LARC) patients. METHODS: Thirty-three patients with LARC underwent total mesorectal excision after preoperative treatment, including 3 cycles of oxaliplatin, raltitrexed, 5-fluorouracil, and folinic acid during pelvic radiotherapy (45 Gy). Staging procedures included endoscopic ultrasound, MRI, and CT. 18F-FDG PET scans were performed at baseline and 12 d after starting radiochemotherapy (intermediate) in all patients. Seventeen patients also had a presurgical scan. For each scan, mean and maximum SUVs were measured. The percentages of SUV decrease from baseline to intermediate (early change) and to presurgical scan (overall change) were assessed and correlated with pathologic response classified as tumor regression grade (TRG). RESULTS: Eighteen tumors (55%) showed complete (TRG1) or subtotal regression (TRG2) and were classified as responders, whereas 15 cases (45%; TRG3 or TRG4) were considered nonresponders. The early median decrease of tumor SUV significantly differed between responders (-62%; range, -44% to -100%) and nonresponders (-22%; range, -2% to -48%). A significant correlation was also found between TRGs and early SUV changes (P < 0.0001). Responders were identified correctly by an early decrease of the mean SUV of > or =52%. CONCLUSION: This study shows that early 18F-FDG PET can predict pathologic response to preoperative treatment. These findings support the usefulness of (18)F-FDG PET during the management with radiochemotherapy of LARC patients.     

Spatial and temporal heterogeneity of regional myocardial uptake in patients without heart disease under fasting conditions on repeated whole-body 18F-FDG PET/CT.

Imaging of cardiac (18)F-FDG uptake is used in the diagnostic evaluation of residual viable myocardium. Although, originally, hibernating myocardium was identified by a mismatch between perfusion defect and relatively preserved (18)F-FDG uptake, at present several studies propose that (18)F-FDG distribution can also be used alone for this purpose. Nevertheless, even severe myocardial (18)F-FDG uptake defects are frequently observed in cancer patients without any cardiac disease. The aim of this study was to retrospectively analyze global and regional (18)F-FDG cardiac images of 49 consecutive cancer patients free of cardiac diseases who submitted to 3 PET scans under fasting conditions. METHODS: Images were acquired with a high-resolution PET/CT scanner. Three-dimensional regions of interest were drawn on the fused PET/CT images to measure the maximal standardized uptake value of the left ventricular myocardium (SUV(Myo)) as well as the average SUV of the left ventricular blood (SUV(LV)) and of the liver (SUV(Liver)). Analysis of regional myocardial (18)F-FDG uptake was performed on a subsample of 26 patients by an automatic recognition of endocardial and epicardial borders and subdividing the left ventricle in 20 segments. Regional (18)F-FDG distribution was defined as the percentage of SUV(Myo) in each region. RESULTS: SUV(Myo) as well as SUV(LV) and SUV(Liver) did not change on average throughout the studies. This stability was not caused by a persistent pattern of myocardial (18-)FDG distribution. Rather, it was associated with important variations in both directions over time. Regional (18)F-FDG distribution was largely heterogeneous in all 3 studies, with a variation coefficient in each patient of 18% +/- 7%, 18% +/- 5%, and 17% +/- 5%, respectively. An (18)F-FDG uptake of <50% occurred in 78, 102, and 69 of 468 segments, although it disappeared in 55% of instances at subsequent examinations. Regional temporal variability was also marked: The absolute value of the difference in percent uptake was 10.1% +/- 7.3% from test 1 to test 2, 8.0% +/- 7.0% from test 1 to test 3, and 9.2% +/- 6.9% from test 2 to test 3. Overall from one test to another, uptake increased or decreased by >10% in 76 and in 116 of 468 segments, respectively. CONCLUSION: The large spatial and temporal heterogeneity of the myocardial metabolic pattern, in cancer patients free of any disease, suggests a word of caution on the use of (18)F-FDG alone as a diagnostic tool for myocardial viability.     

Imaging proliferation in lung tumors with PET: 18F-FLT versus 18F-FDG.

Recently, the thymidine analog 3'-deoxy-3'-(18)F-fluorothymidine (FLT) was suggested for imaging tumoral proliferation. In this prospective study, we examined whether (18)F-FLT better determines proliferative activity in newly diagnosed lung nodules than does (18)F-FDG. METHODS: Twenty-six patients with pulmonary nodules on chest CT were examined with PET and the tracers (18)F-FDG and (18)F-FLT. Tumoral uptake was determined by calculation of standardized uptake value (SUV). Within 2 wk, patients underwent resective surgery or had core biopsy. Proliferative activity was estimated by counting nuclei stained with the Ki-67-specific monoclonal antibody MIB-1 per total number of nuclei in representative tissue specimens. The correlation between the percentage of proliferating cells and the SUVs for (18)F-FLT and (18)F-FDG was determined using linear regression analysis. RESULTS: Eighteen patients had malignant tumors (13 with non-small cell lung cancer [NSCLC], 1 with small cell lung cancer, and 4 with pulmonary metastases from extrapulmonary tumors); 8 had benign lesions. In all visible lesions, mean (18)F-FDG uptake was 4.1 (median, 4.4; SD, 3.0; range, 1.0-10.6), and mean (18)F-FLT uptake was 1.8 (median, 1.2; SD, 2.0; range, 0.8-6.4). Statistical analysis revealed a significantly higher uptake of (18)F-FDG than of (18)F-FLT (Mann-Whitney U test, P < 0.05). (18)F-FLT SUV correlated better with proliferation index (P < 0.0001; r = 0.92) than did (18)F-FDG SUV (P < 0.001; r = 0.59). With the exception of 1 carcinoma in situ, all malignant tumors showed increased (18)F-FDG PET uptake. (18)F-FLT PET was false-negative in the carcinoma in situ, in another NSCLC with a low proliferation index, and in a patient with lung metastases from colorectal cancer. Increased (18)F-FLT uptake was related exclusively to malignant tumors. By contrast, (18)F-FDG PET was false-positive in 4 of 8 patients with benign lesions. CONCLUSION: (18)F-FLT uptake correlates better with proliferation of lung tumors than does uptake of (18)F-FDG and might be more useful as a selective biomarker for tumor proliferation.     

Role of 18F-FDG PET/CT in the prediction of gastric cancer recurrence after curative surgical resection

Purpose

The study evaluated the role of preoperative ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in the prediction of recurrent gastric cancer after curative surgical resection.

Methods

A total of 271 patients with gastric cancer who underwent ¹⁸F-FDG PET/CT and subsequent curative surgical resection were enrolled. All patients underwent follow-up for cancer recurrence with a mean duration of 24?±?12?months. ¹⁸F-FDG PET/CT images were visually assessed and, in patients with positive ¹⁸F-FDG cancer uptake, the maximum standardized uptake value (SUV_max) of cancer lesions was measured. ¹⁸F-FDG PET/CT findings were tested as prognostic factors for cancer recurrence and compared with conventional prognostic factors. Furthermore, ¹⁸F-FDG PET/CT findings were assessed as prognostic factors according to histopathological subtypes.

Results

Of 271 patients, 47 (17?%) had a recurrent event. Positive ¹⁸F-FDG cancer uptake was shown in 149 patients (55?%). Tumour size, depth of invasion, presence of lymph node metastasis, positive ¹⁸F-FDG uptake and SUV_max were significantly associated with tumour recurrence in univariate analysis, while only depth of invasion, positive ¹⁸F-FDG uptake and SUV_max had significance in multivariate analysis. The 24-month recurrence-free survival rate was significantly higher in patients with negative ¹⁸F-FDG uptake (95?%) than in those with positive ¹⁸F-FDG uptake (74?%; p?18F-FDG uptake was a significant prognostic factor in patients with tubular adenocarcinoma (p?=?0.003) or poorly differentiated adenocarcinoma (p?=?0.0001). However, only marginal significance was shown in patients with signet-ring cell carcinoma and mucinous carcinoma (p?=?0.05).

Conclusion

¹⁸F-FDG uptake of gastric cancer is an independent and significant prognostic factor for tumour recurrence. ¹⁸F-FDG PET/CT could provide effective information on the prognosis after surgical resection of gastric cancer, especially in tubular adenocarcinoma and poorly differentiated adenocarcinoma.     

Monitoring isotretinoin therapy in thyroid cancer using 18F-FDG PET

Treatment with isotretinoin (13-cis-retinoic acid, 13-cis-RA) is a recent additional option in advanced, otherwise intractable differentiated thyroid cancers. The aim of this study was to evaluate fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) in the prediction and the monitoring of response to 13-cis-RA therapy. Twenty-one patients with advanced differentiated thyroid cancers were investigated using 18F-FDG PET and iodine-131 whole-body scans before and 3, 6 and 9 months after initiation of 13-cis-RA therapy. After 9 months, 13-cis-RA treatment was discontinued and imaging procedures repeated 3 months later. Average 18F-FDG uptake (SUV) decreased significantly during 13-cis-RA therapy but subsequently increased in five of eight patients after withdrawal of 13-cis-RA. 18F-FDG uptake (SUV) 3 months after onset of 13-cis-RA therapy was significantly lower in patients who developed increased 131I uptake in their tumour sites than in patients with no subsequent increase in 131I uptake. There was no relationship between serum thyroglobulin level on the one hand and simultaneously measured 131I or 18F-FDG uptake on the other hand. There was a tendency towards lower 18F-FDG uptake in tumour manifestations with a better outcome. Therefore, 18F-FDG PET at 3 months after the start of treatment promises to differentiate between those patients who will eventually benefit from 13-cis-RA and those who will not. In conclusion, these data indicate that 18F-FDG PET is a useful tool for the evaluation and monitoring of adjuvant therapy with 13-cis-RA in thyroid cancer.     

18F-FDG uptake as a prognostic variable in primary differentiated thyroid cancer incidentally detected by PET/CT: a multicentre study

Purpose

Our aim was to investigate the association between ¹⁸F-fluorodeoxyglucose (FDG) uptake and event-free survival in patients in whom a differentiated thyroid cancer (DTC) was detected by ¹⁸F-FDG positron emission tomography (PET)/CT.

Methods

Among 884 focal ¹⁸F-FDG PET thyroid incidentalomas referred to our 4 Nuclear Medicine Departments, we investigated 54 patients in whom a DTC was confirmed and a clinical follow-up was available. The ratio between maximum standardized uptake value (SUV_max) of DTC and SUV_mean of the liver (SUV ratio) was recorded for each scan. All patients underwent total thyroidectomy and ¹³¹I remnant ablation. After a median follow-up of 39 months we assessed the outcome. The association between disease persistence/progression, ¹⁸F-FDG uptake and other risk factors (T, N, M and histological subtype) was evaluated through univariate and multivariate analyses.

Results

Of the 54 patients, 39 achieved complete remission. The remaining 15 showed persistence/progression of disease. High ¹⁸F-FDG uptake, i.e. SUV ratio ≥3, showed a low positive predictive value (48 %). Low ¹⁸F-FDG uptake (SUV ratio?<?3) displayed a high negative predictive value (93 %). The median of SUV ratios in T1–T2 (2.2), in M0 (2.7) and in non-virulent subtypes (2.7) were significantly lower (p?<?0.03) than in T3–T4 (5.0), M1 (7.3) and virulent subtypes (6.0). Kaplan-Maier analysis showed a significant association between high ¹⁸F-FDG uptake and disease persistence/progression (p?=?0.001). When we adjusted risk estimates by using a multivariate Cox model, only T (p?=?0.05) remained independently associated with disease persistence/progression.

Conclusion

An intense ¹⁸F-FDG uptake of the primary DTC is associated with persistence/progression of disease. However, when all other prognostic factors have been taken into account, ¹⁸F-FDG uptake does not add further prognostic information.     

Dual-time-point 18F-FDG PET for the evaluation of gallbladder carcinoma.

Conventional imaging techniques such as ultrasonography, CT, and MRI are able to detect gallbladder abnormalities but are not always able to differentiate a malignancy from other disease processes such as cholecystitis. The purpose of the present study was to evaluate the efficacy of dual-time-point (18)F-FDG PET for differentiating malignant from benign gallbladder disease. METHODS: The study evaluated 32 patients who were suspected of having gallbladder tumors. (18)F-FDG PET (whole body) was performed at 62 +/- 8 min (early) after (18)F-FDG injection and was repeated 146 +/- 14 min (delayed) after injection only in the abdominal region. We evaluated the (18)F-FDG uptake both visually and semiquantitatively. Semiquantitative analysis using the standardized uptake value (SUV) was performed for both early and delayed images (SUV(early) and SUV(delayed), respectively). The retention index (RI) was calculated according to the equation (SUV(delayed) - SUV(early)) x 100/SUV(early). The tumor-to-liver ratio was also calculated. Results: The final diagnosis was gallbladder carcinoma in 23 patients and benign disease in 9 patients. For visual analysis of gallbladder carcinoma, delayed (18)F-FDG PET images improved the specificity of diagnosis in 2 patients. When an SUV(early) of 4.5, SUV(delayed) of 2.9, and RI of -8 were chosen as arbitrary cutoffs for differentiating between malignant and benign conditions, sensitivity increased from 82.6% to 95.7% and 100% for delayed imaging and combined early and delayed imaging (i.e., RI), respectively. With the same criteria, specificity decreased from 55.6% to 44.4% for delayed imaging and combined early and delayed imaging, respectively. The specificity of (18)F-FDG PET improved to 80% in the group with a normal level of C-reactive protein (CRP) and decreased to 0% in the group with an elevated CRP level. For gallbladder carcinoma, both SUV and tumor-to-liver ratios derived from delayed images were significantly higher than the ratios derived from early images (P < 0.0001). CONCLUSION: Delayed (18)F-FDG PET is more helpful than early (18)F-FDG PET for evaluating malignant lesions because of increased lesion uptake and increased lesion-to-background contrast. However, the diagnostic performance of (18)F-FDG PET depends on CRP levels.     

Lack of correlation of hypoxic cell fraction and angiogenesis with glucose metabolic rate in non-small cell lung cancer assessed by 18F-Fluoromisonidazole and 18F-FDG PET.

PET offers a noninvasive means to assess neoplasms, in view of its sensitivity and accuracy in staging tumors and potentially in monitoring treatment response. The aim of this study was to evaluate newly diagnosed non-small cell lung cancer (NSCLC) for the presence of hypoxia, as indicated by the uptake of (18)F-Fluoromisonidazole ((18)F-FMISO), and to examine the relationship of hypoxia to the uptake of (18)F-FDG, microvessel density, and other molecular markers of hypoxia. METHODS: Twenty-one patients with suspected or biopsy-proven NSCLC were enrolled prospectively in this study. All patients had PET studies with (18)F-FMISO and (18)F-FDG. Seventeen patients subsequently underwent surgery, with analysis performed for tumor markers of angiogenesis and hypoxia. RESULTS: In the 17 patients with resectable NSCLC (13 men, 4 women; age range, 51-77 y), the mean (18)F-FMISO uptake in tumor was significantly lower than that of (18)F-FDG uptake (P < 0.0001) and showed no correlation with (18)F-FDG uptake (r = 0.26). The mean (95% confidence interval [CI]) (18)F-FMISO SUV(max) (maximum standardized uptake value) was 1.20 [0.95-1.45] compared with the mean [95% CI] (18)F-FDG SUV(max) of 5.99 [4.62-7.35]. The correlation between (18)F-FMISO uptake, (18)F-FDG uptake, and tumor markers of hypoxia and angiogenesis was poor. A weakly positive correlation between (18)F-FMISO and (18)F-FDG uptake and Ki67 was found. CONCLUSION: The hypoxic cell fraction of primary NSCLC is consistently low, and there is no significant correlation in NSCLC between hypoxia and glucose metabolism in NSCLC assessed by (18)F-FDG. These findings have direct implications in understanding the role of angiogenesis and hypoxia in NSCLC biology.     

Prognostic significance of (18)F-FDG and (99m)Tc-methylene diphosphonate uptake in primary osteosarcoma.

The purpose of this retrospective analysis was to evaluate the prognostic significance of both initial glucose metabolism as measured by (18)F-FDG PET and osteoblastic activity as measured by (99m)Tc-methylene diphosphonate (MDP) bone scintigraphy in osteosarcoma. METHODS: In 29 patients (18 male, 11 female; age range, 5-41 y) with primary osteosarcoma, (18)F-FDG uptake and (99m)Tc-MDP uptake were measured semiquantitatively (average and maximum tumor-to-nontumor ratios [T/NT(av) and T/NT(max), respectively]) using PET and bone scintigraphy at the time of diagnosis. After chemotherapy, the patients underwent surgery for their primary tumor, and the response was determined histologically. Cumulative overall survival and event-free survival were determined by clinical and imaging follow-up of 7-72 mo (median, 28 mo). RESULTS: Clinical and imaging follow-up revealed that the disease relapsed or failed to achieve complete remission in 9 patients and that 6 patients died of the disease. Both overall and event-free survival were significantly better in patients with a low (18)F-FDG T/NT(max) (less than the median) than in patients with a high (18)F-FDG T/NT(max) (at least the median). The negative relationship of (18)F-FDG T/NT(av), (99m)Tc-MDP T/NT(max), and (99m)Tc-MDP T/NT(av) with overall and event-free survival did not reach a level of significance. (18)F-FDG uptake values correlated moderately and positively with (99m)Tc-MDP uptake values, but a level of significance was reached only between (18)F-FDG T/NT(max) and (99m)Tc-MDP T/NT(av). CONCLUSION: The initial glucose metabolism of primary osteosarcoma as measured by (18)F-FDG PET using T/NT(max) provides prognostic information. High (18)F-FDG uptake correlates with poor outcome. Thus, (18)F-FDG uptake may be complementary to other well-known factors in judging the prognosis in osteosarcoma.     

Imaging proliferation in brain tumors with 18F-FLT PET: comparison with 18F-FDG.

3'-Deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is a recently developed PET tracer to image tumor cell proliferation. We characterized (18)F-FLT PET of brain gliomas and compared (18)F-FLT with (18)F-FDG PET in side-by-side studies of the same patients. METHODS: Twenty-five patients with newly diagnosed or previously treated glioma underwent PET with (18)F-FLT and (18)F-FDG on consecutive days. Three stable patients in long-term remission were included as negative control subjects. Tracer kinetics in normal brain and tumor were measured. Uptake of (18)F-FLT and (18)F-FDG was quantified by the standardized uptake value (SUV) and the tumor-to-normal tissue (T/N) ratio. The accuracy of (18)F-FLT and (18)F-FDG PET in evaluating newly diagnosed and recurrent gliomas was compared. More than half of the patients underwent resection after the PET study and correlations between PET uptake and the Ki-67 proliferation index were examined. Patients were monitored for a mean of 15.4 mo (range, 12-20 mo). The predictive power of PET for tumor progression and survival was analyzed using Kaplan-Meier statistics. RESULTS: (18)F-FLT uptake in tumors was rapid, peaking at 5-10 min after injection and remaining stable up to 75 min. Hence, a 30-min scan beginning at 5 min after injection was sufficient for imaging. (18)F-FLT visualized all high-grade (grade III or IV) tumors. Grade II tumor did not show appreciable (18)F-FLT uptake and neither did the stable lesions. The absolute uptake of (18)F-FLT was low (maximum-pixel SUV [SUV(max)], 1.33) but image contrast was better than with (18)F-FDG (T/N ratio, 3.85 vs. 1.49). (18)F-FDG PET studies were negative in 5 patients with recurrent high-grade glioma who subsequently suffered tumor progression within 1-3 mo. (18)F-FLT SUV(max) correlated more strongly with Ki-67 index (r = 0.84; P < 0.0001) than (18)F-FDG SUV(max) (r = 0.51; P = 0.07). (18)F-FLT uptake also had more significant predictive power with respect to tumor progression and survival (P = 0.0005 and P = 0.001, respectively). CONCLUSION: Thirty-minute (18)F-FLT PET 5 min after injection was more sensitive than (18)F-FDG to image recurrent high-grade tumors, correlated better with Ki-67 values, and was a more powerful predictor of tumor progression and survival. Thus, (18)F-FLT appears to be a promising tracer as a surrogate marker of proliferation in high-grade gliomas.     

Determination of the prognostic value of [(18)F]fluorodeoxyglucose uptake by using positron emission tomography in patients with non-small cell lung cancer

The aim of this study was to determine whether quantitative information obtained from [(18)F]fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) has a prognostic significance for patients with non-small cell lung cancer (NSCLC). We investigated (18)F-FDG PET imaging of 73 patients with NSCLC. The maximum standardized uptake value (SUV(max)) was significantly different between the histopathological types of tumour (squamous cell carcinoma (n=37, 12.4+/-5.1), adenocarcinoma (n=30, 8.2+/-5.8), bronchioloalveolar carcinoma (n=4, 2.6+/-1.7), <0.01). In the univariate analysis of all patients, staging (P=0.0001), tumour cell type (P=0.013), and a SUV(max) greater than 7 (P=0.0011) was correlated with survival. However, a multivariate analysis identified staging and SUV(max) greater than 7 were affected survival adversely. The mortality rate of patients with group I disease (stage I to stage IIIA) was 5.8 times lower than that of patients with group II disease (stage IIIB to stage IV). Patients with a high SUV(max) (> or =7) had a 6.3 times higher mortality than those with a low SUV(max)(<7). By multivariate analysis of patients with squamous cell carcinoma, only grouping affected survival (P=0.008, relative risk=4.3). In the case of adenocarcinoma, the SUV(max) (>10) correlated exclusively with poorer survival (P=0.031, relative risk=11.152). (18)F-FDG uptake correlated with survival in NSCLC. Especially in adenocarcinomas, the SUV(max) was complementary to other known prognostic factors.     

Detection of hepatocellular carcinoma using 11C-choline PET: comparison with 18F-FDG PET

The purpose of this study was to retrospectively investigate the feasibility of 11C-choline PET, compared with 18F-FDG PET, for the detection of hepatocellular carcinoma (HCC). METHODS: A total of 16 HCC lesions in 12 patients were examined with both 11C-choline PET and 18F-FDG PET. Tumor lesions were identified as areas of focally increased uptake, exceeding that of surrounding noncancerous liver tissue. For semiquantitative analysis, the tumor-to-liver (T/L) ratio was calculated by dividing the maximal standardized uptake value (SUV) in HCC lesions by the mean SUV in noncancerous liver tissue. RESULTS: 11C-choline PET showed a slightly higher detection rate than did 18F-FDG PET for detection of HCC (63% vs. 50%, respectively), although this difference was not statistically significant. 11C-choline PET had a better detection rate for moderately differentiated HCC lesions but not for those poorly differentiated (75% vs. 25%, respectively). In contrast, 18F-FDG PET exhibited the opposite behavior, with corresponding detection rates of 42% and 75%, respectively. The mean 11C-choline SUV and T/L ratio in moderately differentiated HCC lesions were higher than those in poorly differentiated HCC lesions. In contrast, the mean 18F-FDG SUV and T/L ratio in poorly differentiated HCC were higher than those in moderately differentiated HCC. These differences, however, were also not statistically significant. CONCLUSION: 11C-choline PET had a better detection rate for moderately differentiated HCC lesions but not for poorly differentiated HCC lesions, whereas 18F-FDG PET produced the opposite result. 11C-choline is a potential tracer to complement 18F-FDG in detection of HCC lesions.     

Positron emission tomography with 11C-acetate and 18F-FDG in prostate cancer patients

Visualisation of primary prostate cancer, its relapse and its metastases is a clinically relevant problem despite the availability of state-of-the-art methods such as CT, MRI, transrectal ultrasound and fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET). The aim of this study was to evaluate the efficacy of carbon-11 acetate and (18)F-FDG PET in the detection of prostate cancer and its metastases. Twenty-five patients were investigated during the follow-up of primary prostate cancer, suspected relapse or metastatic disease using (11)C-acetate PET; 15 of these patients were additionally investigated using (18)F-FDG PET. Fourteen patients were receiving anti-androgen treatment at the time of the investigation. Lesions were detected in 20/24 (83%) patients using (11)C-acetate PET and in 10/15 (75%) patients using (18)F-FDG PET. Based on the results of both PET scans, one patient was diagnosed with recurrent lung cancer. Median (18)F-FDG uptake exceeded that of (11)C-acetate in distant metastases (SUV =3.2 vs 2.3). However, in local recurrence and in regional lymph node metastases, (11)C-acetate uptake (median SUVs =2.9 and 3.8, respectively) was higher than that of (18)F-FDG (median SUVs =1.0 and 1.1, respectively). A positive correlation was observed between serum PSA level and both (11)C-acetate uptake and (18)F-FDG uptake. (11)C-acetate seems more useful than (18)F-FDG in the detection of local recurrences and regional lymph node metastases. (18)F-FDG, however, appears to be more accurate in visualising distant metastases. There may be a role for combined (11)C-acetate/(18)F-FDG PET in the follow-up of patients with prostate cancer and persisting or increasing PSA.     

Is 18F-3'-fluoro-3'-deoxy-L-thymidine useful for the staging and restaging of non-small cell lung cancer?

The objective of this study was to compare 18F-3'-fluoro-3'-deoxy-L-thymidine (FLT) PET with clinical TNM staging, including that by 18F-FDG PET, in patients with non-small cell lung cancer (NSCLC). METHODS: Patients with NSCLC underwent whole-body 18F-FDG PET and whole-body 18F-FLT PET, using a median of 360 MBq of 18F-FDG (range, 160-500 MBq) and a median of 210 MBq of 18F-FLT (range, 130-420 MBq). 18F-FDG PET was performed 90 min after 18F-FDG injection, and 18F-FLT PET was performed 60 min after 18F-FLT injection. Two viewers independently categorized the localization and intensity of tracer uptake for all lesions. All 18F-FDG PET and 18F-FLT PET lesions were compared. Staging with 18F-FLT PET was compared with clinical TNM staging based on the findings of history, physical examination, bronchoscopy, CT, and 18F-FDG PET. From 8 patients, standardized uptake values (SUVs) were calculated. Maximal SUV and mean SUV were calculated. RESULTS: Sixteen patients with stage IB-IV NSCLC and 1 patient with strong suspicion of NSCLC were investigated. Sensitivity on a lesion-by-lesion basis was 80% for the 8 patients who received treatment before 18F-FLT PET and 27% for the 9 patients who did not receive pretreatment, using 18F-FDG PET as the reference standard. Compared with clinical TNM staging, staging by 18F-FLT PET was correct for 8 of 17 patients: 5 of 9 patients in the group with previous therapy and 3 of 8 patients in the group without previous therapy. The maximal SUV of 18F-FLT PET, at a median of 2.7 and range of 0.8-4.5, was significantly lower than that of 18F-FDG PET, which had a median of 8.0 and range of 3.7-18.8 (n = 8; P = 0.012). The mean SUV of 18F-FLT PET, at a median of 2.7 and range of 1.4-3.3, was significantly lower than that of 18F-FDG PET, which had a median of 6.2 and range of 2.8-13.9 (n = 6; P = 0.027). CONCLUSION: 18F-FLT PET is not useful for staging and restaging NSCLC.     

Whole-body tumor imaging using PET and 2-18F-fluoro-L-tyrosine: preliminary evaluation and comparison with 18F-FDG.

18F-FDG PET imaging is now established as a valuable tool for evaluating cancer patients. However, a limitation of (18)F-FDG is its absence of specificity for tumor. Both protein synthesis and amino acid transport are enhanced in most tumor cells, but their metabolism is less affected in inflammation. We therefore decided to evaluate the ability of PET with 2-(18)F-fluoro-L-tyrosine ((18)F-TYR) to visualize cancer lesions in patients compared with (18)F-FDG PET. METHODS: (18)F-FDG PET and (18)F-TYR PET were performed on 23 patients with histologically proven malignancies (11 non-small cell lung cancers (NSCLCs), 10 lymphomas, and 2 head and neck carcinomas). Fully corrected, whole-body PET studies were obtained on separate days. (18)F-FDG studies were performed after routine clinical fashion. (18)F-TYR studies were started 36 +/- 6 min after tracer injection and a second scan centered over a reference lesion was acquired after completion of the whole-body survey-on average, 87 min after injection. Standardized uptake values (SUVs) were calculated for all abnormal foci and for various normal structures. Results were compared with pathologic or correlative studies. RESULTS: (18)F-FDG PET correctly identified 54 malignant lesions, among which 36 were also visualized with (18)F-TYR (67%). (18)F-TYR did not detect any additional lesion. Tumor SUVs (SUV(bw), 5.2 vs. 2.5), tumor-to-muscle (7.4 vs. 2.7), and tumor-to-mediastinum activity ratios (3 vs. 1.4) were higher with (18)F-FDG than with (18)F-TYR. Two of 11 NSCLCs and 4 of 10 lymphomas were understaged with (18)F-TYR compared with (18)F-FDG. Although the NSCLC lesions missed by (18)F-TYR PET were small, several large lymphoma lesions did not accumulate the tracer. In 4 patients, (18)F-TYR-positive lesions coexisted with (18)F-TYR-negative lesions. There was a high physiologic (18)F-TYR uptake by the pancreas (average SUV(bw), 10.3) and the liver (average SUV(bw), 6.3). Muscle and bone marrow uptakes were also higher with (18)F-TYR than with (18)F-FDG: average SUV(bw), 1 versus 0.7 and 2.6 versus 1.8, respectively. There was no change over time in the (18)F-TYR uptake by the tumors or the normal structures. CONCLUSION: (18)F-TYR PET is not superior to (18)F-FDG PET for staging patients with NSCLC and lymphomas.     

Early prediction of response to chemotherapy in metastatic breast cancer using sequential 18F-FDG PET.

Chemotherapy is currently the treatment of choice for patients with high-risk metastatic breast cancer. Clinical response is determined after several cycles of chemotherapy by changes in tumor size as assessed by conventional imaging procedures including CT, MRI, plain film radiography, or ultrasound. The aim of this study was to evaluate the use of sequential 18F-FDG PET to predict response after the first and second cycles of standardized chemotherapy for metastatic breast cancer. METHODS: Eleven patients with 26 metastatic lesions underwent 31 (18)F-FDG PET examinations (240-400 MBq of 18F-FDG; 10-min 2-dimensional emission and transmission scans). Clinical response, as assessed by conventional imaging after completion of chemotherapy, served as the reference. 18F-FDG PET images after the first and second cycles of chemotherapy were analyzed semiquantitatively for each metastatic lesion using standardized uptake values (SUVs) normalized to patients' blood glucose levels. In addition, whole-body 18F-FDG PET images were viewed for overall changes in the 18F-FDG uptake pattern of metastatic lesions within individual patients and compared with conventional imaging results after the third and sixth cycles of chemotherapy. RESULTS: After completion of chemotherapy, 17 metastatic lesions responded, as assessed by conventional imaging procedures. In those lesions, SUV decreased to 72% +/- 21% after the first cycle and 54% +/- 16% after the second cycle, when compared with the baseline PET scan. In contrast, 18F-FDG uptake in lesions not responding to chemotherapy (n = 9) declined only to 94% +/- 19% after the first cycle and 79% +/- 9% after the second cycle. The differences between responding and nonresponding lesions were statistically significant after the first (P = 0.02) and second (P = 0.003) cycles. Visual analysis of 18F-FDG PET images correctly predicted the response in all patients as early as after the first cycle of chemotherapy. As assessed by 18F-FDG PET, the overall survival in nonresponders (n = 5) was 8.8 mo, compared with 19.2 mo in responders (n = 6). CONCLUSION: In patients with metastatic breast cancer, sequential 18F-FDG PET allowed prediction of response to treatment after the first cycle of chemotherapy. The use of 18F-FDG PET as a surrogate endpoint for monitoring therapy response offers improved patient care by individualizing treatment and avoiding ineffective chemotherapy.