Correlation of <Superscript>18</Superscript>F-FLT and <Superscript>18</Superscript>F-FDG uptake on PET with Ki-67 immunohistochemistry in non-small cell lung cancer

Purpose The nucleoside analogue 3′-deoxy-3′-¹⁸F-fluorothymidine (FLT) has recently been introduced for imaging cell proliferation with positron emission tomography (PET). We prospectively evaluated whether FLT uptake reflects proliferative activity as indicated by the Ki-67 index in non-small cell lung cancer (NSCLC), in comparison with 2-deoxy-2-¹⁸F-fluoro-D-glucose (FDG). Methods A total of 18 patients with newly diagnosed NSCLC were examined with both FLT PET and FDG PET. PET imaging was performed at 60 min after each radiotracer injection. Tumour lesions were identified as areas of focally increased uptake, exceeding background uptake in the lungs. For semi-quantitative analysis, the maximum standardised uptake value (SUV) was calculated. Proliferative activity as indicated by the Ki-67 index was estimated in tissue specimens. Immunohistochemical findings were correlated with SUVs. Results The sensitivity of FLT and FDG PET for the detection of lung cancer was 72% and 89%, respectively. Four of the five false-negative FLT PET findings occurred in bronchiolo-alveolar carcinoma. The mean FLT SUV was significantly lower than the mean FDG SUV. A significant correlation was observed between FLT SUV and Ki-67 index (r = 0.77; p < 0.0002) and for FDG SUV (r = 0.81; p < 0.0001). Conclusion The results of this preliminary study suggest that, compared with FDG, FLT may be less sensitive for primary staging in patients with NSCLC. Although FLT uptake correlated significantly with proliferative activity in NSCLC, the correlation was not better than that for FDG uptake.     

Normal uptake of <Superscript>18</Superscript>F-FDG in the testis: an assessment by PET/CT

Objective The aim of this study was to assess the physiological uptake of ¹⁸F-fluoro-2-deoxyglucose (FDG) by an apparently normal testis with combined positron emission tomography–computed tomography (PET/CT) and its correlation with age, blood glucose level, and testicular volume. Methods The testicular uptake of ¹⁸F-FDG, expressed as the standardized uptake value (SUV), was measured on PET/CT images in 203 men. The correlation between SUV and age, blood glucose level, and testicular volume was assessed. Results The SUV in the total of 406 testes was 2.44 ± 0.45 (range 1.23–3.85). The SUV was 2.81 ± 0.43 (2.28–3.85) for 30–39 years (n = 12), 2.63 ± 0.45 (1.77–3.75) for 40–49 years (n = 64), 2.46 ± 0.35 (1.44–3.15) for 50–59 years (n = 82), 2.51 ± 0.41 (1.50–3.46) for 60–69 years (n = 86), 2.43 ± 0.47 (1.42–3.29) for 70–79 years (n = 86), and 2.18 ± 0.45 (1.23–3.03) for 80–89 years (n = 76). When we calculated the mean SUV of bilateral testes in each patient, there were significant statistical differences between those in the age group of 30–39 years and 80–89 years, 40–49 years and 80–89 years, and 50–60 years and 80–89 years, when using an unpaired test with Bonferroni correction. The laterality index (|L − R|/(L + R) × 2) in 203 men was 0.066 ± 0.067 (0–0.522). There was a mild correlation between the mean SUV and age (r = −0.284, P < 0.001) as well as between the mean SUV and mean volume (r = +0.368, P < 0.001). There was no correlation between the mean SUV and glucose blood level (r = −0.065, P = 0.358). Conclusions Some uptake of FDG is observed in the normal testis and declines slightly with age. Physiological FDG uptake in the testis should not be confused with pathological accumulation.     

Detection of gastric cancer using <Superscript>18</Superscript>F-FLT PET: comparison with <Superscript>18</Superscript>F-FDG PET

Purpose  We prospectively investigated the feasibility of 3′-deoxy-3′-¹⁸F-fluorothymidine (FLT) positron emission tomography (PET) for the detection of gastric cancer, in comparison with 2-deoxy-2-¹⁸F-fluoro-d-glucose (FDG) PET, and determined the degree of correlation between the two radiotracers and proliferative activity as indicated by Ki-67 index. Methods  A total of 21 patients with newly diagnosed advanced gastric cancer were examined with FLT PET and FDG PET. Tumour lesions were identified as areas of focally increased uptake, exceeding that of surrounding normal tissue. For semiquantitative analysis, the maximal standardized uptake value (SUV) was calculated. Results  For detection of advanced gastric cancer, the sensitivities of FLT PET and FDG PET were 95.2% and 95.0%, respectively. The mean (±SD) SUV for FLT (7.0 ± 3.3) was significantly lower than that for FDG (9.4 ± 6.3 p < 0.05). The mean FLT SUV and FDG SUV in nonintestinal tumours were higher than in intestinal tumours, although the difference was not statistically significant. The mean (±SD) FLT SUV in poorly differentiated tumours (8.5 ± 3.5) was significantly higher than that in well and moderately differentiated tumours (5.3 ± 2.1; p < 0.04). The mean FDG SUV in poorly differentiated tumours was higher than in well and moderately differentiated tumours, although the difference was not statistically significant. There was no significant correlation between Ki-67 index and either FLT SUV or FDG SUV. Conclusion  FLT PET showed as high a sensitivity as FDG PET for the detection of gastric cancer, although uptake of FLT in gastric cancer was significantly lower than that of FDG.     

Accumulation of [<Superscript>11</Superscript>C]acetate in normal prostate and benign prostatic hyperplasia: comparison with prostate cancer

Carbon-11 acetate positron emission tomography (PET) has been reported to be of clinical value for the diagnosis of prostate cancer. However, no detailed analysis has yet been carried out on the physiological accumulation of [(11)C]acetate in the prostate. The purpose of this study was to elucidate the physiological accumulation of [(11)C]acetate in the prostate using dynamic PET. The study included 30 subjects without prostate cancer [21 with normal prostate and nine with benign prostatic hyperplasia (BPH)] and six patients with prostate cancer. A dynamic PET study was performed for 20 min after intravenous administration of 555 MBq of [(11)C]acetate. The standardised uptake value (SUV) at 16-20 min post tracer administration and the early-to-late-activity ratio of the SUV (E/L ratio), which was determined by dividing the SUV(6-10 min) by the SUV(16-20min), were calculated to evaluate the accumulation of [(11)C]acetate. The prostate was clearly visualised and distinguished from adjacent organs in PET images in most of the cases. The SUV of the prostate (2.6+/-0.8) was significantly higher than that of the rectum (1.7+/-0.4) or bone marrow (1.3+/-0.3) ( P<0.0001 in each case). The SUV of the normal prostate of subjects aged <50 years (3.4+/-0.7) was significantly higher than both the SUV for the normal prostate of subjects aged > or =50 years (2.3+/-0.7) and that of subjects with BPH (2.1+/-0.6) ( P<0.01 in each case). The primary prostate cancer in six cases was visualised by [(11)C]acetate PET. However, the difference in the SUV between subjects aged > or =50 with normal prostate or with BPH and the patients with prostate cancer (1.9+/-0.6) was not statistically significant. There was also no significant difference in the E/L ratio between subjects aged > or =50 with normal prostate (0.98+/-0.04) or BPH (0.96+/-0.08) and patients with prostate cancer (1.02+/-0.12). In conclusion, a normal prostate exhibits age-related physiological accumulation of [(11)C]acetate. Careful interpretation of [(11)C]acetate PET images of prostate cancer is necessary because the SUV and the E/L ratio for the normal prostate and for BPH overlap significantly with those for prostate cancer.     

<Superscript>11</Superscript>C-acetate PET imaging of lung cancer: comparison with <Superscript>18</Superscript>F-FDG PET and <Superscript>99m</Superscript>Tc-MIBI SPET

Recently carbon-11 acetate (AC) positron emission tomography (PET) has been reported to be of clinical value for the diagnosis of cancer that is negative on fluorine-18 fluorodeoxyglucoce (FDG) PET. We investigated the uptake of AC in lung cancer to determine whether this tracer is of potential value for tumour detection and characterisation, and to compare AC PET imaging with FDG PET and technetium-99m sestamibi (MIBI) single-photon emission tomography (SPET). Twenty-three patients with 25 lung cancers underwent AC and FDG PET. Twenty of 23 patients were also investigated with MIBI SPET. Dynamic images were acquired for 26 min after the injection of 555 MBq of AC. Standardised uptake values (SUVs) and/or tumour to non-tumour activity ratios (T/N) for each tumour were investigated at 10–20 min after AC administration, 40–60 min after administration of 185 MBq FDG and 15–45 min after administration of 555 MBq MIBI. Twenty lung cancers were resected surgically, and the degree of tracer uptake in the primary lesion was correlated with histopathological features (cell dedifferentiation and aggressiveness) and prognosis. Rapid uptake of AC followed by extremely slow clearance was observed. For the purpose of tumour identification, AC PET was inferior to FDG PET in 8 of 25 (32%) lung cancers, and the T/N of AC was lower than that of FDG. However, AC PET was superior to FDG PET in the identification of a slow-growing tumour (bronchiolo-alveolar carcinoma). There was a positive correlation between AC uptake (T/N) and MIBI uptake (T/N) (r=0.799, P<0.0001). A positive correlation was not observed between either AC or MIBI uptake and the degree of cell dedifferentiation in lung adenocarcinomas, whereas FDG uptake did correlate with the degree of cell dedifferentiation. In lung adenocarcinoma, there was a weak correlation between aggressiveness and FDG uptake, but no correlation was evident for AC and MIBI. In addition, a positive correlation was not observed between AC or MIBI uptake and postoperative recurrence in lung adenocarcinoma, whereas FDG uptake did correlate with postoperative recurrence. Thus, the greater the FDG uptake, the higher the malignant grade. In conclusion, for the purpose of tumour identification, AC PET was inferior to FDG PET but superior to MIBI SPET. Neither AC nor MIBI uptake reflects the malignant grade in lung adenocarcinoma, whereas FDG uptake does. AC PET is less diagnostically informative than FDG PET in patients with lung cancer. However, AC PET may play a complementary role in the identification of low-grade malignancies that are not FDG avid.     

Intrasubject correlation between static sean and distribution volume images for [11C]flumazenil PET

Accumulation of [11C]flumazenil (FMZ) reflects central nervous system benzodiazepine receptor (BZR). We searched for the optimal time for a static PET scan with FMZ as semi-quantitative imaging of BZR distribution. In 10 normal subjects, a dynamic series of decay-corrected PET scans was performed for 60 minutes, and the arterial blood was sampled during the scan to measure radioactivity and labeled metabolites. We generated 13 kinds of "static scan" images from the dynamic scan in each subject, and analyzed the pixel correlation for these images versus distribution volume (DV) images. We also analyzed the time for the [11C]FMZ in plasma and tissue to reach the equilibrium. The intra-subject pixel correlation demonstrated that the "static scan" images for the period centering around 30 minutes post-injection had the strongest linear correlation with the DV image. The ratio of radioactivity in the cortex to that in the plasma reached a peak at 40 minutes after injection. Considering the physical decay and patient burden, we conclude that the decay corrected static scan for [11C]FMZ PET as semi-quantitative imaging of BZR distribution is to be optimally acquired from 20 to 40 minutes after injection.     

Assessment of the metabolic activity of bone grafts with <Superscript>18</Superscript>F-fluoride PET

Purpose The aims of this prospective study were to evaluate quantitative approaches to ¹⁸F-fluoride positron emission tomography (PET) imaging in allogenic bone grafts of the limbs, and to assess the time course of graft healing after surgery.Methods We performed a total of 52 dynamic ¹⁸F-fluoride PET studies in 34 patients with cancellous and full bone grafts. Seven patients were imaged three times at 6, 12, and 24 months after surgery, and four patients were imaged twice. PET data were quantitatively analyzed using non-linear regression (NLR) analysis, Patlak analysis, and standardized uptake value (SUV).Results Fluoride bone metabolism in cancellous grafts decreased by 25% from 6 to 12 months post surgery, and revealed a total decrease of 60–65% after 2 years for SUV, K_Pat, and K_NLR. Full bone grafts first showed an increase by 20% from 6 to 12 months and from then on decreased to 70% of the initial activity at the end of 2 years with either quantification method. In two patients with non-union of their full bone grafts, increases in SUV, K_Pat, K_NLR, and K₁ far above average and outside the normal time pattern were observed. Highly significant correlations were found between SUV, K_Pat, K_NLR, and K₁ for both grafts and normal limb bones. In patients imaged repeatedly, the percentage changes in fluoride graft metabolism were also significantly correlated between SUV, K_Pat, and K_NLR.Conclusion Quantitative ¹⁸F-fluoride PET is a promising tool for assessment of fluoride metabolism and normal healing in bone grafts of the limbs.     

Intraindividual comparison of <Superscript>68</Superscript>Ga-DOTA-TATE and <Superscript>18</Superscript>F-DOPA PET in patients with well-differentiated metastatic neuroendocrine tumours

Aim  To compare the diagnostic impact of ⁶⁸Ga-DOTA-TATE and ¹⁸F-DOPA PET in the diagnosis of well-differentiated metastatic neuroendocrine tumours (NET). Methods  PET/CT using both ⁶⁸Ga-DOTA-TATE and ¹⁸F-DOPA was performed in 25 patients with histologically proven metastatic NET (nine gut, five pancreas, six lung, one paranasal sinus, four with unknown primary). Analyses of PET examinations were patient-based (pathological uptake: yes/no), and based on tumour regions (primary tumour if present and metastases of liver, lung, bones and lymph nodes). The results were compared with the results of contrast enhanced CT, and with plasma serotonin levels, which were available in 24 of the 25 patients. Results  Patient-based sensitivities were 96% for ⁶⁸Ga-DOTA-TATE PET and 56% for ¹⁸F-DOPA PET. ⁶⁸Ga-DOTA-TATE PET delineated metastases in 54 of 55 positive metastatic tumour regions in contrast to 29 of 55 delineated by ¹⁸F-DOPA PET. Overall, ⁶⁸Ga-DOTA-TATE was superior to ¹⁸F-DOPA in 13 patients (two patients showed fewer positive tumour regions with ¹⁸F-DOPA PET). The results were comparable in 12 patients. In 13 of 24 patients, plasma serotonin levels were elevated, and 11 of these 13 patients showed pathological uptake of ¹⁸F-DOPA. Of the 11 patients with normal levels of serotonin, 3 also showed positive ¹⁸F-DOPA uptake. In patients positive for ¹⁸F-DOPA uptake the maximum tumour SUVs were correlated with the levels of serotonin (r=0.66, p=0.01). Conclusion  In this study ⁶⁸Ga-DOTA-TATE PET proved clearly superior to ¹⁸F-DOPA PET for detection and staging of NET. ¹⁸F-DOPA uptake tended to be increased in those patients with elevated plasma serotonin. We conclude that ¹⁸F-DOPA PET should be employed in patients with NET with negative ⁶⁸Ga-DOTA-TATE PET and elevated plasma serotonin.     

Differentiation of hepatocellular adenoma and focal nodular hyperplasia using <Superscript>18</Superscript>F-fluorocholine PET/CT

The aim of this pilot study was to evaluate the use of PET/CT with ¹⁸F-fluorocholine in the differentiation of hepatocellular adenoma (HCA) from focal nodular hyperplasia (FNH). Patients with liver lesions larger than 2 cm suspicious for HCA or FNH were prospectively included. All patients underwent PET/CT with ¹⁸F-fluorocholine and histopathological diagnosis was obtained by either liver biopsy or surgery. The ratios between the maximum standardized uptake value (SUV) of the lesion and the mean SUV of normal liver parenchyma were calculated and a receiver operating characteristic (ROC) curve analysis was performed. Ten patients with FNH and 11 with HCA were included. The mean SUV ratio was 1.68±0.29 (±SD) for FNH and 0.88±0.18 for HCA (p<0.001). An SUV ratio cut-off value between 1.12 and 1.22 differentiated patients with FNH from those with HCA with 100% sensitivity and 100% specificity. This pilot study showed that PET/CT with ¹⁸F-fluorocholine can differentiate HCA from FNH.     

Correlation of immunohistopathological expression of somatostatin receptor 2 with standardised uptake values in <Superscript>68</Superscript>Ga-DOTATOC PET/CT

Purpose  In clinical routine somatostatin analogue positron emission tomography/computed tomography (PET/CT) such as ⁶⁸Ga-DOTA-Tyr-octreotide (DOTATOC)-PET/CT could substitute conventional ¹¹¹In-Octreotide scintigraphy. Immunohistochemistry (IHC) for somatostatin receptor 2 (SSTR2) might be a tool to predict positivity of ⁶⁸Ga-DOTATOC in patients where initial staging was not performed, e.g., in incidental findings. We therefore compared a score of SSTR2-IHC with the in vivo standard uptake value (SUV) of preoperative or prebiopsy ⁶⁸Ga-DOTATOC PET/CT. Materials and methods  In 18 patients, ⁶⁸Ga-DOTATOC PET/CT scans were quantified with SUV calculations and correlated to a cell membrane-based SSTR2-IHC score (ranging from 0 to 3). Results  Negative IHC scores were consistent with SUV values below 10. Furthermore, all score 2 and 3 specimens corresponded with high SUV values (above 15). Conclusion  SSTR2-IHC scores correlated well with SUV values and we propose to use SSTR2 immunohistochemistry in patients missing a preoperative PET scan to indicate ⁶⁸Ga-DOTATOC-PET/CT as method for restaging and follow-up in individual patients.     

Kinetic modelling of [<Superscript>11</Superscript>C]flumazenil using data-driven methods

Purpose  [¹¹C]Flumazenil (FMZ) is a benzodiazepine receptor antagonist that binds reversibly to central-type gamma-aminobutyric acid (GABA-A) sites. A validated approach for analysis of [¹¹C]FMZ is the invasive one-tissue (1T) compartmental model. However, it would be advantageous to analyse FMZ binding with whole-brain pixel-based methods that do not require a-priori hypotheses regarding preselected regions. Therefore, in this study we compared invasive and noninvasive data-driven methods (Logan graphical analysis, LGA; multilinear reference tissue model, MRTM2; spectral analysis, SA; basis pursuit denoising, BPD) with the 1T model. Methods  We focused on two aspects: (1) replacing the arterial input function analyses with a reference tissue method using the pons as the reference tissue, and (2) shortening the scan protocol from 90 min to 60 min. Dynamic PET scans were conducted in seven healthy volunteers with arterial blood sampling. Distribution volume ratios (DVRs) were selected as the common outcome measure. Results  The SA, LGA with and without arterial input, and MRTM2 agreed best with the 1T model DVR values. The invasive and noninvasive BPD were slightly less well correlated. The full protocol of a 90-min emission data performed better than the 60-min protocol, but the 60-min protocol still delivered useful data, as assessed by the coefficient of variation, and the correlation and bias analyses. Conclusion  This study showed that the SA, LGA and MRTM2 are valid methods for the quantification of benzodiazepine receptor binding with [¹¹C]FMZ using an invasive or noninvasive protocol, and therefore have the potential to reduce the invasiveness of the procedure.     

Disease activity and 18F-FDG uptake in organising pneumonia: semi-quantitative evaluation using computed tomography and positron emission tomography

Purpose: The present study was conducted to evaluate whether ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) in combination with computed tomography (CT) reflects disease activity in patients with organising pneumonia.Methods: Eighty-eight subjects who were normal (n=66) or who had proven organising pneumonia (n=22) underwent FDG-PET and CT imaging. The subjects included 55 men and 33 women, ranging in age from 24 to 63 years (mean 47 years). PET and CT data sets were digitally fused using a conformational PET/CT fusion algorithm. All scans were evaluated independently by two chest radiologists who were unaware of other clinical data. The visual score, maximal and mean standardised uptake value (SUV), and maximal and mean lesion-to-normal tissue ratio (LNR) were calculated. The imaging results were compared with the laboratory and pulmonary function test results. The inflammatory cells in the lesions were quantified immunohistochemically.Results: The visual score, maximal and mean SUV, and maximal and mean LNR of the patients with organising pneumonia were significantly higher than those of the normal subjects. The patients with air-space consolidation had a significantly higher SUV than those without air-space consolidation (mean±SD 3.08±0.39 vs 2.35±0.56; p<0.05). The number of CD45⁺ cells was positively correlated with the maximal SUV (r=0.632, p<0.01) and the maximal LNR (r=0.453, p<0.05). The number of CD8⁺ T lymphocytes also showed positive correlations with the maximal SUV (r=0.540, p<0.01) and the maximal LNR (r=0.547, p<0.01).Conclusion: Patients with organising pneumonia have an enhanced FDG accumulation which reflects the degree of disease activity.     

Dual-time-point <Superscript>18</Superscript>F-FDG PET imaging for diagnosis of disease type and disease activity in patients with idiopathic interstitial pneumonia

Purpose  Individual clinical courses of idiopathic interstitial pneumonia (IIP) are variable and difficult to predict because the pathology and disease activity are contingent, and chest computed tomography (CT) provides little information about disease activity. In this study, we applied dual-time-point [¹⁸F]-fluoro-2-deoxy-D-glucose (¹⁸F-FDG) positron emission tomography (PET), commonly used for diagnosis of malignant tumours, to the differential diagnosis and prediction of disease progression in IIP patients. Methods  Fifty patients with IIP, including idiopathic pulmonary fibrosis (IPF, n = 21), non-specific interstitial pneumonia (NSIP, n = 18) and cryptogenic organizing pneumonia (COP, n = 11), underwent ¹⁸F-FDG PET examinations at two time points: scan 1 at 60 min (early imaging) and scan 2 at 180 min (delayed imaging) after ¹⁸F-FDG injection. The standardized uptake values (SUV) at the two points and the retention index (RI-SUV) calculated from them were evaluated and compared with chest CT findings, disease progression and disease types. To evaluate short-term disease progression, all patients were examined by pulmonary function test every 3 months for 1 year after ¹⁸F-FDG PET scanning. Results  The early SUV for COP (2.47 ± 0.74) was significantly higher than that for IPF (0.99 ± 0.29, p = 0.0002) or NSIP (1.22 ± 0.44, p= 0.0025). When an early SUV cut-off value of 1.5 and greater was used to distinguish COP from IPF and NSIP, the sensitivity, specificity and accuracy were 90.9, 94.3 and 93.5%, respectively. The RI-SUV for IPF and NSIP lesions was significantly greater in patients with deteriorated pulmonary function after 1 year of follow-up (progressive group, 13.0 ± 8.9%) than in cases without deterioration during the 1-year observation period (stable group, −16.8 ± 5.9%, p < 0.0001). However, the early SUV for all IIP types provided no additional information of disease progression. When an RI-SUV cut-off value of 0% and greater was used to distinguish progressive IIPs from stable IIPs, the sensitivity, specificity and accuracy were 95.5, 100 and 97.8%, respectively. Conclusion  Early SUV and RI-SUV obtained from dual-time-point ¹⁸F-FDG PET are useful parameters for the differential diagnosis and prediction of disease progression in patients with IIP.     

Clinical evaluation of the effect of attenuation correction technique on<Superscript>18</Superscript>F-fluoride PET images

OBJECTIVE: The purpose of this study is to evaluate effect of attenuation correction technique on 18F-fluoride positron emission tomography (PET). METHODS: We performed PET scans after the injection of 185 MBq 18F-fluoride on 32 patients from October 20th, 2004 to April 13th, 2005. We calculated bone-to-muscle ratios for the images with and without attenuation correction. We placed regions of interest (ROIs) on normal bone accumulation in 22 patients. The exclusion criteria were bone metastasis, Paget's disease, and rheumatoid arthritis. Several regions were chosen for ROI placement: skull, cervical vertebra, mandible, scapula, thoracic vertebra, rib, humerus, lumbar vertebra, radius, ulna, pelvis, femoral head, femoral shaft, tibia, and fibula. The count ratios of normal bones to gluteus muscle were calculated as bone-to-muscle ratios. The count ratios of abnormal skeletal lesions to gluteus muscles were calculated as bone-to-muscle ratios, while the count ratios of abnormal skeletal lesions to normal bones were calculated as bone-to-bone ratios. RESULTS: PET images without attenuation correction showed significantly higher mean bone-to-muscle ratios than those with attenuation correction (p < 0.05) for all normal bones except the femoral head and lumbar vertebrae. For abnormal bones, bone-to-muscle ratios without attenuation correction were significantly higher than those with attenuation correction (p < 0.005). The same statistical significance was found for bone-to-bone ratios (p < 0.005). CONCLUSIONS: The attenuation correction technique is not necessary to conduct the visual interpretation of 18F-fluoride PET images. The bone-to-muscle ratio analysis without attenuation correction may be of use to differentiate malignant from benign disease processes.     

<Superscript>11</Superscript>C-methionine (MET) and <Superscript>18</Superscript>F-fluorothymidine (FLT) PET in patients with newly diagnosed glioma

Purpose  The purpose of this prospective study was to clarify the individual and combined role of l-methyl-¹¹C-methionine-positron emission tomography (MET-PET) and 3′-deoxy-3′-[¹⁸F]fluorothymidine (FLT)-PET in tumor detection, noninvasive grading, and assessment of the cellular proliferation rate in newly diagnosed histologically verified gliomas of different grades. Materials and methods  Forty-one patients with newly diagnosed gliomas were investigated with MET-PET before surgery. Eighteen patients were also examined with FLT-PET. MET and FLT uptakes were assessed by standardized uptake value of the tumor showing the maximum uptake (SUV_max), and the ratio to uptake in the normal brain parenchyma (T/N ratio). All tumors were graded by the WHO grading system using surgical specimens, and the proliferation activity of the tumors were determined by measuring the Ki-67 index obtained by immunohistochemical staining. Results  On semiquantitative analysis, MET exhibited a slightly higher sensitivity (87.8%) in tumor detection than FLT (83.3%), and both tracers were 100% sensitive for malignant gliomas. Low-grade gliomas that were false negative on MET-PET also were false negative on FLT-PET. Although the difference of MET SUV_max and T/N ratio between grades II and IV gliomas was statistically significant (P < 0.001), there was a significant overlap of MET uptake in the tumors. The difference of MET SUV_max and T/N ratio between grades II and III gliomas was not statistically significant. Low-grade gliomas with oligodendroglial components had relatively high MET uptake. The difference of FLT SUV_max and T/N ratio between grades III and IV gliomas was statistically significant (P < 0.01). Again, the difference of FLT SUV_max and T/N ratio between grades II and III gliomas was not statistically significant. Grade III gliomas with non-contrast enhancement on MR images had very low FLT uptake. In 18 patients who underwent PET examination with both tracers, a significant but relatively weak correlation was observed between the individual SUV_max of MET and FLT (r = 0.54, P < 0.05) and T/N ratio of MET and FLT (r = 0.56, P < 0.05). Total FLT uptake in the tumor had a higher correlation (r = 0.89, P < 0.001) with Ki-67 proliferation index than MET uptake (r = 0.49, P < 0.01). Conclusions  PET studies using MET and FLT are useful for tumor detection in newly diagnosed gliomas. However, there is no complimentary information in tumor detection with simultaneous measurements of MET- and FLT-PET in low grade gliomas. FLT-PET seems to be superior than MET-PET in noninvasive tumor grading and assessment of proliferation activity in gliomas of different grades.     

Impact of dual-time-point <Superscript>18</Superscript>F-FDG PET imaging and partial volume correction in the assessment of solitary pulmonary nodules

Purpose Our aim was to assess the diagnostic potential of ¹⁸F-FDG PET using partial volume correction and dual-time-point imaging in the assessment of solitary pulmonary nodules. Methods We included 265 patients in this retrospective study (171 men; 94 women; age range, 41–92 years). All had pulmonary nodules on CT, and diagnosis was confirmed by biopsy or follow-up CT. All underwent whole body FDG PET, 60 min after FDG injection. Of the 265 patients, 255 underwent second FDG PET for chest 100 min after injection. Maximum SUVs for nodules were calculated from both scans. Partial volume correction for first time SUVs was applied, using coefficient factor. Malignancy was defined using the following criteria: (1) Visual assessment; (2) First time SUV ≥ 2.5; (3) Partial volume corrected first time SUV ≥ 2.5; (4) second time SUV ≥ 2.5; (5) Increase in SUV over time; (6) Increase or no change in SUV; (7) First time SUV ≥ 2.5 and/or increase or no change in SUV. Results Biopsy and follow-up revealed 72 malignant lung nodules and 193 benign nodules. Sensitivity, specificity and accuracy for the five criteria were as follows: (1) 97, 58 and 68%; (2) 65, 92 and 85%; (3) 84, 91 and 89%; (4) 90, 80 and 83%; (5) 84, 95 and 92%; (6) 92, 92, and 92%; (7) 95, 90 and 91%, respectively. Conclusion Dual-time-point ¹⁸F-FDG PET has potential impact on improving the diagnostic accuracy for malignant lung nodules. Dual-time-point ¹⁸F-FDG PET imaging should be included in the clinical work-up of patients with pulmonary nodule.     

<Superscript>11</Superscript>C-methionine uptake in cerebrovascular disease: A comparison with<Superscript>18</Superscript>F-FDG PET and<Superscript>99m</Superscript>Tc-HMPAO SPECT

OBJECTIVES: Carbon-11-L-methyl-methionine (11C-methionine) has been reported to be useful for evaluating brain tumors, but several other brain disorders have also shown signs of high methionine uptake. We retrospectively evaluated the significance of 11C-methionine uptake in cerebrovascular diseases, and also compared our results with those for 18F-FDG PET and 99mTc-HMPAO SPECT. METHODS: Seven patients, including 3 patients with a cerebral hematoma and 4 patients with a cerebral infarction, were examined. All 7 patients underwent both 11C-methionine PET and 99mTc-HMPAO SPECT, and 6 of them underwent 18F-FDG PET. RESULTS: A high 11C-methionine uptake was observed in all 3 patients with cerebral hematoma. Increased 99mTc-HMPAO uptake was observed in 2 out of 3 patients, and all 3 patients had decreased 18F-FDG uptake. Of 4 patients with a cerebral infarction, high 11C-methionine uptake was observed in 3. Increased 99mTc-HMPAO uptake was also observed in one patient, whereas 3 patients had decreased 18F-FDG uptake. CONCLUSIONS: We should keep in mind that high 11C-methionine uptake is frequently observed in cerebrovascular diseases. CVD should therefore be included in the differential diagnosis when encounting patients with a high 11C-methionine uptake.     

Diagnostic impact of PET with <Superscript>18</Superscript>F-FDG, <Superscript>18</Superscript>F-DOPA and 3-<Emphasis Type="Italic">O</Emphasis>-methyl-6-[<Superscript>18</Superscript>F]fluoro-DOPA in recurrent or metastatic medullary thyroid carcinoma

Purpose In patients with medullary thyroid carcinoma (MTC), rising levels of the tumour markers calcitonin and CEA after primary surgery indicate tumour recurrence or metastases. The only chance of cure is the resection of localised tumour tissue. For positron emission tomography (PET) with ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) and ¹⁸F-dihydroxyphenylalanine (¹⁸F-DOPA), sensitivities of 78% and 63% have been reported, but in a considerable percentage of MTC patients the source of tumour marker elevation is not detected. The aim of this retrospective data evaluation was to compare the value of PET with ¹⁸F-FDG, ¹⁸F-DOPA and the amino acid tracer 3-O-methyl-6-[¹⁸F]fluoro-DOPA (¹⁸F-OMFD) in the detection of MTC recurrence. Methods Fifteen patients with elevated calcitonin were investigated with PET as part of their individual clinical work-up. All patients underwent ¹⁸F-FDG PET and ¹⁸F-DOPA PET, and ten patients underwent ¹⁸F-OMFD PET. Results With ¹⁸F-FDG, seven patients showed foci in the neck, mediastinum, upper abdomen or bone. In seven patients, ¹⁸F-DOPA revealed suspicious foci; five of these seven patients showed partially corresponding uptake of ¹⁸F-FDG in the neck and mediastinum. Two of these patients underwent surgery and metastases were verified. With ¹⁸F-OMFD, a small focus in the liver was suspected in one patient without a correlate on ¹⁸F-FDG PET, ¹⁸F-DOPA PET or conventional imaging. Conclusion ¹⁸F-FDG and ¹⁸F-DOPA showed foci that were highly suspicious for local recurrence or metastasis of MTC, although histological verification in these patients with numerous previous surgical interventions was performed in only two patients. The amino acid tracer ¹⁸F-OMFD had no diagnostic impact in these patients.     

The dopamine D<Subscript>2</Subscript> receptor ligand <Superscript>18</Superscript>F-desmethoxyfallypride: an appropriate fluorinated PET tracer for the differential diagnosis of parkinsonism

For therapeutic and prognostic reasons it is important to differentiate between idiopathic parkinsonian syndrome (IPS, Parkinsons disease) and atypical parkinsonian syndromes (APS) like multiple system atrophy or progressive supranuclear palsy. Whereas IPS patients usually show a normal or upregulated postsynaptic dopamine D₂ receptor profile, APS patients present decreased postsynaptic tracer binding. The aim of this prospective study was to evaluate the D₂ receptor antagonist fluorine-18 desmethoxyfallypride (¹⁸F-DMFP), a recently developed positron emission tomography (PET) tracer with better clinical availability than carbon-11 raclopride, for the differential diagnosis of IPS versus APS. The study included 16 healthy control subjects and 35 patients with clinically diagnosed parkinsonism (16 IPS patients, 19 APS patients). All patients underwent PET imaging after injection of 180–200 MBq ¹⁸F-DMFP. Receiver operating characteristic (ROC) analyses were performed in order to assess the diagnostic performance of ¹⁸F-DMFP PET. We found the striatal ¹⁸F-DMFP uptake ratio to be significantly (P<0.01) reduced in the APS patients (2.44±0.42) compared with the healthy control subjects (3.61±0.43) and the IPS patients (3.21±0.78), whereas the uptake ratios of the IPS patients and the control subjects did not differ significantly. For the differential diagnosis of APS versus IPS, the ROC analysis of caudate ¹⁸F-DMFP binding showed a specificity, sensitivity and accuracy of 100%, 74% and 86%, respectively, as well as positive and negative predictive values of 100% and 76%, respectively. Based on these first clinical results, we consider ¹⁸F-DMFP to be an appropriate PET tracer for the differential diagnosis of parkinsonian syndromes, with the advantage of better clinical availability than ¹¹C-labelled D₂ radioligands.     

Mean and maximum standardized uptake values in [<Superscript>18</Superscript>F]FDG-PET for assessment of histopathological response in oesophageal squamous cell carcinoma or adenocarcinoma after radiochemotherapy

Purpose  To evaluate the potential of [¹⁸F]fluorodeoxyglucose positron emission tomography (FDG-PET) for the assessment of histopathological response and survival after neoadjuvant radiochemotherapy in patients with oesophageal cancer. Patients and methods  In 2005 and 2006, 55 patients (43 men, 12 women; median age 60 years) with locally advanced oesophageal cancer (cT3-4 Nx M0; 24 with squamous cell carcinoma, 31 with adenocarcinoma) underwent transthoracic en bloc oesophagectomy after completion of treatment with cisplatin, 5-fluorouracil, and radiotherapy ad 36 Gy in a prospective clinical trial. Of the 55 patients, 21 (38%) were classified as histopathological responders (<10% vital residual tumour cells) and 34 (62%) as nonresponders. FDG-PET was performed before (PET 1) and 3–4 weeks after the end (PET 2) of radiochemotherapy with assessment of maximum and average standardized uptake values (SUV) for correlation with histopathological response and survival. Results  Histopathological responders had a slightly higher baseline SUV than nonresponders (p<0.0001 between PET 1 and PET 2 for responders and nonresponders) and the decrease was more prominent in responders. Except for SUVmax in patients with squamous cell carcinoma neither baseline nor preoperative SUV nor percent SUV reduction correlated significantly with histopathological response. Histopathological responders had a 2-year overall survival of 91 ± 9% and nonresponders a survival of 53 ± 10% (p = 0.007). Conclusion  Our study does not support recent reports that FDG-PET predicts histopathological response and survival in patients with locally advanced oesophageal cancer treated by neoadjuvant radiochemotherapy. An erratum to this article can be found at