Dual-time point PET/CT with F-18 FDG for the differentiation of malignant and benign bone lesions

Purpose  The purpose of the present study was to evaluate whether 2-fluoro[fluorine-18]-2-deoxy-d-glucose (F-18 FDG) positron emission tomography (PET) could differentiate malignant and benign bone lesions and whether obtaining delayed F-18 FDG PET images could improve the accuracy of the technique. Methods  In a prospective study, 67 patients with bone lesions detected by computed tomography (CT) or magnetic resonance imaging were included. Whole body PET/CT imaging was performed at 1 h (early) after the F-18 FDG injection and delayed imaging at 2 h post injection was performed only in the abnormal region. Semiquantitative analysis was performed using maximum standardized uptake value (SUV_max), obtained from early and delayed images (SUV_maxE and SUV_maxD, respectively). The retention index (RI) was calculated according to the equation: RI = (SUV_maxD − SUV_maxE) × 100/SUV_maxE. Histopathology of surgical specimens and follow-up data were used as reference criteria. The SUV_maxE and RI were compared between benign and malignant lesions. Results  The final diagnoses revealed 53 malignant bone lesions in 37 patients and 45 benign lesions in 30 patients. There were statistically significant differences in the SUV_maxE between the malignant and benign lesions (P = 0.03). The mean SUV_maxE was 6.8 ± 4.7 for malignant lesions and 4.5 ± 3.3 for benign lesions. However, a considerable overlap in the SUV_maxE was observed between some benign and malignant tumors. With a cutoff value of 2.5 for the SUV_maxE, the sensitivity, specificity, and accuracy were 96.0%, 44.0%, and 72.4%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) were 67.1% and 90.9%, respectively. There were significant differences in the RI between the malignant and benign lesions (P = 0.004). But there was overlap between the two groups. The mean RI was 7 ± 11 for the benign lesions and 18 ± 11 for the malignant lesions. When an RI of 10 was used as the cutoff point, the sensitivity, specificity, and accuracy were 90.6%, 76.0%, and 83.7.0%, respectively. The PPV and NPV were 81.4% and 87.1%, respectively. Conclusions  The results of this study indicate that dual-time point F-18 FDG PET may provide more help in the differentiation of malignant tumors from benign ones.     

[<Superscript>18</Superscript>F]FDG-PET predicts complete pathological response of breast cancer to neoadjuvant chemotherapy

Purpose To evaluate, in breast cancer patients treated by neoadjuvant chemotherapy, the predictive value of reduction in FDG uptake with regard to complete pathological response (pCR). Methods Forty-seven women with non-metastatic, non-inflammatory, large or locally advanced breast cancer were included. Tumour uptake of FDG was evaluated before and after the first course of neoadjuvant chemotherapy. Four indices were used: maximal and average SUV without or with correction by body surface area and glycaemia (SUV_max, SUV_avg, SUV_max-BSA-G and SUV_avg-BSA-G, respectively). The predictive value of reduction in FDG uptake with respect to pCR was studied by logistic regression analysis. Relationships between baseline [¹⁸F]FDG uptake and prognostic parameters were assessed. Results The relative decrease in FDG uptake (ΔSUV) after the first course of neoadjuvant chemotherapy was significantly greater in the pCR group than in the non-pCR group (p < 0.000066). The four FDG uptake indices were all strongly correlated with each other. A decrease in SUV_max-BSA-G of 85.4% ± 21.9% was found in pCR patients, versus 22.6% ± 36.6% in non-pCR patients. ΔSUV_max-BSA-G <−60% predicted the pCR with an accuracy of 87% and ΔSUVs were found to be only factors predictive of the pCR at multivariate analysis. An elevated baseline SUV was associated with high mitotic activity (p < 0.0016), tumour grading (p < 0.004), high nuclear pleomorphism score (p < 0.03) and negative hormonal receptor status (p < 0.005). Conclusion In breast cancer patients, after only one course of neoadjuvant chemotherapy the reduction in FDG uptake is an early and powerful predictor of pCR.     

<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.     

Nonionic intravenous contrast agent does not cause clinically significant artifacts to <Superscript>18</Superscript>F-FDG PET/CT in patients with lung cancer

Objective This study was performed to evaluate the effects of intravenous (i.v.) contrast agent on semi-quantitative values and lymph node (LN) staging of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) in patients with lung cancer. Methods Thirty-five patients with lung cancer were prospectively included. Whole-body PET and nonenhanced CT images were acquired 60 min following the i.v. injection of 370 MBq ¹⁸F-FDG and subsequently, enhanced-CT images were acquired with the i.v. administration of 400 mg iodinated contrast agent without positional change. PET images were reconstructed with both nonenhanced and enhanced CTs, and the maximum and average standardized uptake values (SUV_max and SUV_ave) calculated from lung masses, LNs, metastatic lesions, and normal structures were compared. To evaluate the effects of the i.v. contrast agent on LN staging, we compared the LN status on the basis of SUVs (cut-offs; SUV_max = 3.5, SUV_ave = 3.0). Results The mean differences of SUV_max in normal structures between enhanced and nonenhanced PET/CT were 15.23% ± 13.19% for contralateral lung, 8.53% ± 6.11% for aorta, 5.85% ± 4.99% for liver, 5.47% ± 6.81% for muscle, and 2.81% ± 3.05% for bone marrow, and those of SUV_ave were 10.17% ± 9.00%, 10.51% ± 7.89%, 4.95% ± 3.89%, 5.66% ± 9.12%, and 2.49% ± 2.50%, respectively. The mean differences of SUV_max between enhanced and nonenhanced PET/CT were 5.89% ± 3.92% for lung lesions (n = 41), 6.27% ± 3.79% for LNs (n = 76), and 3.55% ± 3.38% for metastatic lesions (n = 35), and those of SUV_ave were 3.22% ± 3.01%, 2.86% ± 1.71%, and 2.33% ± 3.95%, respectively. Although one LN status changed from benign to malignant because of contrast-related artifact, there was no up- or down-staging in any of the patients after contrast enhancement. Conclusions An i.v. contrast agent may be used in PET/CT without producing any clinically significant artifact.     

[<Superscript>11</Superscript>C]choline PET/CT imaging in occult local relapse of prostate cancer after radical prostatectomy

Purpose The aim of this study was to assess the accuracy and clinical impact of [¹¹C]choline PET/CT for localizing occult relapse of prostate adenocarcinoma after radical prostatectomy. Methods Fourty-nine patients with prostate adenocarcinoma, radical prostatectomy, no evidence of metastatic disease, and occult relapse underwent [¹¹C]choline PET/CT. Thirty-six of the patients had biochemical evidence and histological evaluation of local recurrence. Thirteen patients had PSA < 0.3 ng/ml and no evidence of active disease after 1 year follow-up. Focal nodular [¹¹C]choline uptake in the prostatic fossa was visually assessed and graded on a five point scale. Maximum standardized radioactivity uptake value (SUV_max) and the lesion size were measured. A receiver operating characteristic (ROC) analysis was performed and the clinical impact of the PET/CT study was determined. Results [¹¹C]choline PET/CT was true positive in 23/33 patients and true negative in 12/13 controls. SUV_max of local recurrence was 3.0 (median, range 0.6–7.4) and 1.1 (0.4–1.6) in controls (p = 0.0002). Lesion size was 1.7 cm (range 0.9–3.7). Area under the ROC curve for detecting relapse was 0.90 ± 0.05 and 0.83 ± 0.06 for visual evaluation and SUV_max, respectively. Sensitivity and specificity of [¹¹C]choline PET/CT were 0.73 and 0.88, respectively. [¹¹C]choline PET/CT identified 12/17 (71%) patients with a favourable biochemical response to local radiotherapy at 2 year (median, 0.8–3.2 range) follow-up. Conclusions Focally increased [¹¹C]choline uptake in the prostatic bed reliably predicted local low volume occult relapsing prostate adenocarcinoma after radical prostatectomy and identified 71% of patients with a favourable biochemical response to local radiotherapy.     

Dual-time-point <Superscript>18</Superscript>F-FDG PET/CT in the diagnosis of solitary pulmonary lesions in a region with endemic granulomatous diseases

Objective

Granulomatous diseases (GDs) can be metabolically active and indistinguishable from lung cancer on ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) imaging. Evaluation of solitary pulmonary lesions remains a diagnostic challenge in regions with endemic GD. This study sought to determine the efficacy of dual-time-point (DTP) ¹⁸F-FDG PET/computed tomography (CT) imaging in diagnosing solitary pulmonary lesions from such regions.

Methods

A total of 50 patients with solitary pulmonary nodules or masses with confirmed histopathological diagnoses underwent DTP ¹⁸F-FDG PET/CT imaging at 1 and 3 h after tracer injection. The maximum standardized uptake value (SUV_max) on early and delayed scans (SUV_1h and SUV_3h, respectively) and retention index (RI) were calculated for each pulmonary lesion. Receiver operating characteristic analysis was performed to evaluate the discriminating validity of the parameters.

Results

There were 37 malignant and 13 benign solitary pulmonary lesions. Eight of the 13 (62 %) benign lesions were GDs. The sensitivity/specificity/accuracy of SUV_1h, SUV_3h and RI were 84/69/80 %, 84/85/84 %, and 81/54/74 %, respectively. SUV_3h had the best diagnostic performance, especially regarding specificity. The values of SUV_1h and SUV_3h were significantly different between malignant lesions and GD, while the RI values of malignant lesions and GD were both high (18.6 ± 19.5 and 18.7 ± 15.3 %, respectively; P = not significant).

Conclusion

SUV_3h appeared to improve the diagnostic specificity of ¹⁸F-FDG PET/CT in evaluating solitary pulmonary lesions from regions with endemic GD.

     

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.     

FET PET for the evaluation of untreated gliomas: correlation of FET uptake and uptake kinetics with tumour grading

Purpose Treatment and prognosis of gliomas depend on their histological tumour grade. The aim of the study was to evaluate the potential of [¹⁸F]fluoroethyltyrosine (FET) PET for non-invasive tumour grading in untreated patients. Methods Dynamic FET PET studies were performed in 54 patients who, based on MRI, were estimated to have low grade (LG; n = 20), intermediate (WHO II–III; n = 4) or high grade (HG; n = 30) tumours. For standard evaluation, tumour SUV_max and the ratio to background (SUV_max/BG) were calculated (sum image: 20–40 min). For dynamic evaluation, mean SUV values within a 90% isocontour ROI (SUV90) and the SUV90/BG ratios were determined for each time frame to evaluate the course of FET uptake. Results were correlated with histopathological findings from PET-guided stereotactic biopsies. Results Histology revealed gliomas in all patients. Using the standard method a statistically significant difference (p = 0.001) was found between LG (n = 20; SUV_max/BG: 2.16 ± 0.98) and HG (n = 34; SUV_max/BG: 3.29 ± 1.06) gliomas (opt. threshold 2.58: SN71%/SP85%/area under ROC curve [AUC]:0.798), however, with a marked overlap between WHO II to IV tumours. Time activity curves showed slight increase in LG, whereas HG tumours presented with an early peak (10–20 min) followed by a decrease. Dynamic evaluation successfully separated LG from HG gliomas with higher diagnostic accuracy (SN94%/SP100%/AUC:0.967). Conclusions Based on the ratio-based method, a statistically significant difference was found between LG and HG gliomas. Due to the interindividual variability, however, no reliable individual grading was possible. In contrast, dynamic evaluation allowed LG and HG gliomas to be differentiated with high diagnostic power and, thus, should supplement the conventional method.     

The clinical efficacy of <Superscript>18</Superscript>F-FDG-PET/CT in benign and malignant musculoskeletal tumors

Objective  Most of the current clinical data on the role of 2-[¹⁸F]fluoro-2-deoxy-d-glucose positron emission tomography (¹⁸F-FDG-PET) in musculoskeletal tumors come from patients studied with PET and less frequently with hardware fusion PET/computed tomography (CT). And the number of cases in each report is too small to clarify the exact clinical efficacy of PET or PET/CT. This prompted us to analyze our experience with ¹⁸F-FDG-PET/CT in a relatively large group of patients with musculoskeletal tumors. Methods   ¹⁸F-FDG-PET/CT was performed on 91 patients from May 2004 to June 2007. The final diagnosis was obtained from surgical biopsy in 83 patients (91%) and clinical follow-up in 8 (9%). We analyzed the characteristics and amount of ¹⁸F-FDG uptake in soft tissue and bone tumors, and investigated the ability of ¹⁸F-FDG-PET/CT to differentiate malignant from benign tumors. The cutoff maximum standardized uptake value (SUV_max) was calculated using the receiver-operation characteristic curve method. Sensitivity, specificity, and diagnostic accuracy were calculated with cutoff SUV_max and the final diagnosis. Unpaired t test was used for the statistical analysis. Results  Final diagnosis revealed 19 benign soft tissue tumors (mean SUV_max 4.7), 27 benign bone tumors (5.1), 25 malignant soft tissue tumors (8.8), and 20 malignant bone tumors (10.8). There was a significant difference in SUV_max between benign and malignant musculoskeletal tumors in total (P < 0.002), soft tissue tumors (P < 0.05), and bone tumors (P < 0.02). Sensitivity, specificity, and diagnostic accuracy were 80%, 65.2%, and 73% in total with cutoff SUV_max 3.8, 80%, 68.4%, and 75% in the soft tissue tumors with cutoff SUV_max 3.8, and 80%, 63%, and 70% in the bone tumors with cutoff SUV_max 3.7. Conclusions   ¹⁸F-FDG-PET/CT reliably differentiated malignant soft tissue and bone tumors from benign ones, although there were many false-positive and falsenegative lesions. Further studies with all kinds of musculoskeletal tumors in large numbers are needed to improve the diagnostic accuracy of ¹⁸F-FDG-PET/CT.     

Heterogeneity of intrahepatic fat distribution determined by <Superscript>18</Superscript>F-FDG PET and CT

Objectives

Hepatic steatosis is common but less is known of the heterogeneity of hepatic fat distribution and its clinical significance. Our objective was to measure the regional variabilities within the liver of standardised uptake values (SUV) as potential markers of hepatic fat distribution heterogeneity.

Methods

Twenty-four patients having routine, clinically indicated PET/CT with ¹⁸F-FDG and a wide range of fatty liver severity were selected. Maximum SUV (SUV_max), average SUV (SUV_ave), both calculated using lean body mass, and CT density were measured in 12 × 2-cm diameter ROIs in each patient. SUV_ave was also measured over the left ventricular cavity (SUV_LV). Mean values of SUV indices, their ratios with SUV_LV, and CT density in the 12 ROIs were calculated. Regional variabilities of SUV indices were expressed as coefficients of variation (CV; standard deviation/mean). Body mass index (BMI) was estimated from height and body weight, and %body fat and lean body mass from height, weight and gender.

Results

Mean SUV_max/SUV_ave correlated significantly with mean CT density (r = ?0.51; p < 0.02). In contrast, mean SUV_max, mean SUV_ave and their ratios with SUV_LV showed no correlation with CT density. Mean CT density correlated with weight (r = ?0.59; p < 0.005), BMI (r = ?0.57; p < 0.01) and %body fat (r = ?0.49; p < 0.02). Corresponding correlation coefficients for mean SUV_max/SUV_ave were 0.74 (p < 0.001), 0.65 (p < 0.001) and 0.46 (p < 0.03). In contrast, mean SUV_max, mean SUV_ave and their ratios with SUV_LV showed no correlation with BMI, weight and %body fat. The CV of SUV_max/SUV_ave (r = ?0.67; p < 0.001), but not the CVs of SUV_max or SUV_ave, correlated with mean CT density.

Conclusions

SUV_max/SUV_ave and CT density are markers of hepatic steatosis. The regional variability of SUV_max/SUV_ave may be a marker of hepatic fat distribution heterogeneity. The novel concept is introduced that hepatic fat distribution heterogeneity may be a marker of hepatic pathology and of clinical value, and deserves further exploration with texture analysis.

     

Assessment of intra- and interobserver reproducibility of rest and cold pressor test-stimulated myocardial blood flow with <Superscript>13</Superscript>N-ammonia and PET

Purpose We investigated the intraobserver reproducibility of myocardial blood flow (MBF) measurements with PET at rest and during cold pressor test (CPT), and the interobserver agreement. Methods Twenty normal volunteers were studied. Using ¹³N-ammonia, MBF was measured at rest and during CPT and measurement was repeated in a 1-day session (short-term reproducibility; SR). After a follow-up of 2 weeks, MBF was measured again at rest and during CPT and compared with the initial baseline measurement (long-term reproducibility; LR). In addition, adenosine-induced hyperemic MBF increases were assessed. Results Assessment of the SR did not show a significant absolute difference in MBF at rest, MBF during CPT or the endothelium-related change in MBF from rest to CPT (ΔMBF) (0.09 ± 0.10, 0.11 ± 0.09, and 0.08 ± 0.05 ml/g/min; p = NS), and they were linearly correlated (r = 0.72, r = 0.76 and r = 0.84; p < 0.0001). Corresponding values for standard error of the estimate (SEE), as indicative for the range of MBF measurement error, were 0.14, 0.14, and 0.09 ml/g/min. The LR yielded relatively higher but non-significant absolute differences in the MBF at rest, MBF during CPT and ΔMBF (0.10 ± 0.10, 0.14 ± 0.10, and 0.19 ± 0.10 ml/g/min; p = NS), and paired MBFs significantly correlated (r = 0.75, r = 0.71, and r = 0.60; p < 0.001). Corresponding SEEs were 0.13, 0.15, and 0.16 ml/g/min. The interobserver analysis yielded a high correlation for MBF at rest, MBF during CPT, and hyperemic MBF (r = 0.96, SEE=0.04; r = 0.78, SEE=0.11; and r = 0.87, SEE=0.28; p < 0.0001, respectively), and also a good interobserver correlation for ΔMBF (r = 0.62, SEE=0.09; p < 0.003). Conclusion Short- and long-term MBF responses to CPT, as an index for endothelium-related coronary vasomotion, can be measured reproducibly with ¹³N-ammonia PET. In addition, the high interobserver reproducibility for repeat analysis of MBF values suggests the measurements to be largely operator independent. Thomas H. Schindler and Xiao-Li Zhang contributed equally to this paper.     

Target volume definition for <Superscript>18</Superscript>F-FDG PET-positive lymph nodes in radiotherapy of patients with non-small cell lung cancer

Purpose FDG PET is increasingly used in radiotherapy planning. Recently, we demonstrated substantial differences in target volumes when applying different methods of FDG-based contouring in primary lung tumours (Nestle et al., J Nucl Med 2005;46:1342–8). This paper focusses on FDG-positive mediastinal lymph nodes (LN_PET). Methods In our institution, 51 NSCLC patients who were candidates for radiotherapy prospectively underwent staging FDG PET followed by a thoracic PET scan in the treatment position and a planning CT. Eleven of them had 32 distinguishable non-confluent mediastinal or hilar nodal FDG accumulations (LN_PET). For these, sets of gross tumour volumes (GTVs) were generated at both acquisition times by four different PET-based contouring methods (visual: GTV_vis; 40% SUV_max: GTV₄₀; SUV=2.5: GTV_2.5; target/background (T/B) algorithm: GTV_bg). Results All differences concerning GTV sizes were within the range of the resolution of the PET system. The detectability and technical delineability of the GTVs were significantly better in the late scans (e.g. p = 0.02 for diagnostic application of SUV_max = 2.5; p = 0.0001 for technical delineability by GTV_2.5; p = 0.003 by GTV₄₀), favouring the GTV_bg method owing to satisfactory overall applicability and independence of GTVs from acquisition time. Compared with CT, the majority of PET-based GTVs were larger, probably owing to resolution effects, with a possible influence of lesion movements. Conclusion For nodal GTVs, different methods of contouring did not lead to clinically relevant differences in volumes. However, there were significant differences in technical delineability, especially after early acquisition. Overall, our data favour a late acquisition of FDG PET scans for radiotherapy planning, and the use of a T/B algorithm for GTV contouring.     

Early detection and monitoring of cartilage alteration in the experimental meniscectomised guinea pig model of osteoarthritis by <Superscript>99m</Superscript>Tc-NTP 15-5 scintigraphy

Purpose This study in the meniscectomised guinea pig aimed to demonstrate that the radiotracer ^99mTc-NTP 15-5 would have pathophysiological validity for in vivo osteoarthritis imaging. Methods The specificity of ^99mTc-NTP 15-5 for cartilage was determined in healthy animals (n = 13), by tissue radioactivity counting, joint autoradiography and scintigraphy. ^99mTc-NTP 15-5 scintigraphy was performed at 20, 50, 80, 115, 130, 150 and 180 days after medial meniscectomy (n = 10 MNX) or sham operation (n = 5), and scintigraphic ratios (operated/contralateral) were calculated for femoral (F) and tibial (T) areas. F and T ratios were compared with those of ^99mTc-MDP bone scintigraphy. At the study end-point, autoradiographic analysis of joint ^99mTc-NTP 15-5 distribution and macroscopic scoring of cartilage integrity were performed. Results The high and specific accumulation of ^99mTc-NTP 15-5 in normal cartilage (about 5.5 ± 1.7 % of injected dose/g of tissue), which permitted joint imaging with high contrast, was affected by osteoarthritis. In the MNX group, ^99mTc-NTP 15-5 accumulation in cartilage within the operated joint, relative to the contralateral joint, was observed to change in the same animals as pathology progressed. Although F and T ratios were significantly higher in MNX (F = 1.7 ± 0.2; T = 1.6 ± 0.1) than in shams (F = 1.0 ± 0.1; T = 1.0 ± 0.1) at day 50, they were significantly lower in MNX (F = 0.6 ± 0.1; T = 0.7 ± 0.1) than in shams (F = 1.0 ± 0.1; T = 0.9 ± 0.1) at day 180. No change in ^99mTc-MDP uptake was observed over 6 months. Macroscopic analysis confirmed features of osteoarthritis only in MNX knees. Conclusion These results in MNX guinea pigs provide additional support for the use of ^99mTc-NTP 15-5 for in vivo imaging of osteoarthritis.     

Prognostic value of pre-treatment <Superscript>18</Superscript>F-FDG-PET uptake in small-cell lung cancer

Purpose

Small-cell lung cancer (SCLC) is an aggressive disease, despite an initially favorable response to treatment, and its prognosis is still poor. Multiple parameters have been studied as possible prognostic factors, but none of them are reliable enough to change the treatment approach. ¹⁸F-fluorodeoxyglucose-positron emission tomography (FDG-PET) is a novel imaging technique for staging of SCLC. The aim of this study was to evaluate the prognostic value of pre-treatment FDG-PET parameters on clinical outcome in limited stage (LS) SCLC patients treated with curative thoracic radiotherapy (RT) and chemotherapy.

Methods

Clinical records of 46 LS-SCLC patients with pre-treatment FDG-PET imaging were retrospectively reviewed. Patients were treated with definitive RT for a total dose of 50–60 Gy and chemotherapy. The clinical endpoints were progression-free survival (PFS) and overall survival (OS).

Results

The median age was 59 (range 30–82) years, and median follow-up time was 23.2 months (range 5–82.8 months). Median OS was 30.9 months for pre-treatment tumor maximum standardized uptake value (SUV_max) <9.3 and 20.6 months for SUV_max ≥9.3 (p = 0.027) and PFS was 55.6 months for SUV_max <9.3 and 38.6 months for SUV_max ≥9.3 (p = 0.16). Median OS was 73 months for pre-treatment lymph node SUV_max <5.8 and 21 months for ≥5.8 (p = 0.01) and PFS was 38.6 months (range 6.8–70.3 months) for SUV_max-LN ≥5.8; all patients with SUV_max-LN <5.8 were alive (p = 0.07). Median survival time was 28.2 months (range 21.7–34.7 months) for patients younger than 65 and 8.7 months (range 5.7–11.8 months) for those ≥65 years (p = 0.00).

Conclusions

Pre-treatment FDG-PET uptake may be a valuable tool to evaluate prognosis in SCLC patients. Patients with a higher pre-treatment FDG uptake may be considered at increased risk of failure and may benefit from more aggressive treatment approaches.

     

Simultaneous evaluation of myocardial blood flow,cardiac function and lung water content using [<Superscript>15</Superscript>O]H<Subscript>2</Subscript>O and positron emission tomography

Purpose This study sought to evaluate an imaging approach using [¹⁵O]H₂O and positron emission tomography (PET) for simultaneous assessment of myocardial perfusion, cardiac function and lung water content as a potential indicator of pulmonary oedema. Methods Twenty-six subjects divided into two groups (group I, 13 patients with idiopathic dilated cardiomyopathy; group II, 13 healthy volunteers) underwent dynamic PET scanning after intravenous infusion of ≈995 MBq [¹⁵O]H₂O. In both groups, echocardiograms were performed after the PET studies. From the dynamic [¹⁵O]H₂O data, lung water content (LWC) at equilibrium, myocardial blood flow (MBF), cardiac output (CO), stroke volume (SV) and stroke volume indexes (SVI) using the indicator dilution principle were determined. Results LWC was 18% (p = 0.038) higher in patients than in controls. Global MBF did not differ significantly between the groups, but regional MBF values were significantly lower (p < 0.05) in the anterior and septal walls in the patient group. The results of the Passing-Bablok regression indicated the absence of a systematic difference between the two techniques. Bland-Altman analysis performed for each group (patients vs healthy controls) showed a non-significant bias (p > 0.1) of −0.02 ± 0.82 vs −0.05 ± 0.54 l/min (CO), −1.44 ± 14.31 vs 1.70 ± 10.56 ml/beat (SV) and 0.47 ± 6.21 vs 0.30 ± 5.02 ml/beat/m² (SVI). The 95% limits of agreement were −1.62 to 1.59 vs −1.11 to 1.01 l/min (CO), −26.61 to 29.49 vs −22.39 to 18.99 ml/beat (SV) and −11.69 to 12.88 vs −9.53 to 10.14 ml/beat/m² (SVI). Right ventricular CO was increased by 33% (p = 0.014) in the patient group as compared with normal controls. Conclusion Our results demonstrate that additional analysis of cardiac function and lung water content are feasible from the dynamic cardiac [¹⁵O]H₂O PET studies acquired for myocardial perfusion. The parameters appear to work as expected. Further studies are warranted to elucidate the clinical value of these new parameters. This study was financially supported by grants from Turku University Hospital (EVO) and Finnish Foundation for Cardiovascular Research.     

Pulmonary <Superscript>18</Superscript>F-FDG uptake helps refine current risk stratification in idiopathic pulmonary fibrosis (IPF)

Purpose

There is a lack of prognostic biomarkers in idiopathic pulmonary fibrosis (IPF) patients. The objective of this study is to investigate the potential of ¹⁸F-FDG-PET/ CT to predict mortality in IPF.

Methods

A total of 113 IPF patients (93 males, 20 females, mean age?±?SD: 70?±?9 years) were prospectively recruited for ¹⁸F-FDG-PET/CT. The overall maximum pulmonary uptake of ¹⁸F-FDG (SUV_max), the minimum pulmonary uptake or background lung activity (SUV_min), and target-to-background (SUV_max/ SUV_min) ratio (TBR) were quantified using routine region-of-interest analysis. Kaplan–Meier analysis was used to identify associations of PET measurements with mortality. We also compared PET associations with IPF mortality with the established GAP (gender age and physiology) scoring system. Cox analysis assessed the independence of the significant PET measurement(s) from GAP score. We investigated synergisms between pulmonary ¹⁸F-FDG-PET measurements and GAP score for risk stratification in IPF patients.

Results

During a mean follow-up of 29 months, there were 54 deaths. The mean TBR?±?SD was 5.6?±?2.7. Mortality was associated with high pulmonary TBR (p?=?0.009), low forced vital capacity (FVC; p?=?0.001), low transfer factor (TLCO; p?<?0.001), high GAP index (p?=?0.003), and high GAP stage (p?=?0.003). Stepwise forward-Wald–Cox analysis revealed that the pulmonary TBR was independent of GAP classification (p?=?0.010). The median survival in IPF patients with a TBR < 4.9 was 71 months, whilst in those with TBR?> 4.9 was 24 months. Combining PET data with GAP data (“PET modified GAP score”) refined the ability to predict mortality.

Conclusions

A high pulmonary TBR is independently associated with increased risk of mortality in IPF patients.

     

Usefulness of <Superscript>18</Superscript>F-fluorodeoxyglucose positron emission tomography for diagnosing disease activity and monitoring therapeutic response in patients with pulmonary mycobacteriosis

Purpose  To evaluate the usefulness of ¹⁸F-FDG PET in the imaging of pulmonary lesions related to disease activity and in monitoring responses to treatment in patients with pulmonary mycobacteriosis (PM). Materials and methods  We used high-resolution computed tomography (HRCT) and ¹⁸F-FDG PET to evaluate 47 consecutive untreated patients with PM, 25 with tuberculosis (TB) and 22 with Mycobacterium avium-intracellulare complex (MAC), who presented with small peripheral pulmonary nodules ≤3 cm, and compared the findings. The diagnosis of mycobacteriosis was confirmed by bacteriological examinations of bronchoscopic or surgically resected specimens. PET scans were visually and quantitatively analysed using SUVmax. In addition, 14 patients with PM underwent repeat PET scanning during antimycobacterial therapy, and changes in ¹⁸F-FDG uptake were clinically evaluated (6 during treatment and 12 after treatment). Results  Of all the lesions, 87.2% had SUVmax levels ranging from 3 to 7 (5.05 ± 1.56, range 2.5–7.6, n = 47). Further, SUV levels in patients with PM reflected disease activity as estimated by HRCT, but did not differ significantly between those with TB (4.96 ± 1.61, n = 25) and MAC (5.15 ± 1.53, n = 22). ¹⁸F-FDG uptake was significantly decreased in all 14 patients who received chemotherapy, indicating a positive response to treatment. Conclusion   ¹⁸F-FDG PET is considered to be useful for the diagnosis and evaluation of disease activity along with HRCT findings, and in monitoring response to chemotherapy in patients with PM.     

Pilot prospective evaluation of <Superscript>18</Superscript>F-FPPRGD<Subscript>2</Subscript> PET/CT in patients with cervical and ovarian cancer

Purpose

We report the effect of antiangiogenic therapy on the biodistribution of ¹⁸F-FPPRGD₂ (a surrogate biomarker of integrin α_vβ₃ expression), and the potential of ¹⁸F-FPPRGD₂ to predict the prognosis in patients with cervical cancer and ovarian cancer in this clinical scenario.

Methods

Data from six women, age range 30 – 59 years (mean?±?SD 44.0?±?12.5 years), who had undergone a ¹⁸F-FPPRGD₂ PET/CT scan and bevacizumab-containing therapy were prospectively collected and analyzed. We compared baseline ¹⁸F-FPPRGD₂ and ¹⁸F-FDG uptake in the lesions and tumor-to-background (T/B) ratios. The maximum and mean ¹⁸F-FPPRGD₂ standardized uptake values (SUV_max and SUV_mean) were recorded for 13 normal organs, as well as in all the identified malignant lesions on the pretreatment scan and the 1-week post-treatment scan. We also measured changes in ¹⁸F-FPPRGD₂ uptake from before to 1 week after treatment_, and compared them to the changes in ¹⁸F-FDG uptake from before to 6 weeks after treatment. Treatment outcomes were correlated with these changes.

Results

The uptake in lesions and T/B ratio of ¹⁸F-FPPRGD₂ were lower than those of ¹⁸F-FDG (SUV_max 3.7?±?1.3 vs. 6.0?±?1.8, P?<?0.001; SUV_mean 2.6?±?0.7 vs. 4.2?±?1.3, P?<?0.001; T/B ratio based on SUV_max 2.4?±?1.0 vs. 2.6?±?1.0, P?<?0.04; T/B ratio based on SUV_mean 1.9?±?0.6 vs. 2.4?±?1.0, P?<?0.003). One patient did not return for the follow-up scan and in another patient no lesions were identified on the pretreatment scan. ¹⁸F-FPPRGD₂ uptake in lesions in the remaining four patients had significantly changed 1 week after treatment (SUV_mean 3.3?±?1.0 vs. 2.7?±?1.0, P?<?0.001), while uptake in all normal tissues analyzed was not affected by treatment. One patient with clinical disease progression had a decrease in lesional ¹⁸F-FPPRGD₂ SUV_mean of 1.6 % and in ¹⁸F-FDG SUV_mean of 9.4 %. Two patients with a clinical complete response to treatment had decreases in lesional ¹⁸F-FPPRGD₂ SUV_mean of 25.2 % and 25.0 % and in ¹⁸F-FDG SUV_mean of 6.1 % and 71.8 %. One patient with a clinical partial response had a decrease in lesional ¹⁸F-FPPRGD₂ SUV_mean of 7.9 % and in ¹⁸F-FDG SUV_mean of 76.4 %.

Conclusion

This pilot study showed that ¹⁸F-FPPRGD₂ and ¹⁸F-FDG provide independent information about the biology of ovarian and cervical cancers. Bevacizumab-containing therapy does not affect ¹⁸F-FPPRGD₂ uptake in normal organs, but does result in statistically significant changes in lesions. In addition, ¹⁸F-FPPRGD₂ may have potential for early prediction of response to such treatments. These preliminary findings have to be confirmed in larger studies.

     

<Superscript>18</Superscript>F-FDG and <Superscript>18</Superscript>F-FLT PET/CT imaging in the characterization of mediastinal lymph nodes

Purpose

There is currently no single modality for accurate characterization of enlarged mediastinal lymph nodes into benign or malignant. Recently ¹⁸F-fluorothymidine (FLT) has been used as a proliferation marker. In this prospective study, we examined the role of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) and ¹⁸F-FLT PET/CT in categorizing mediastinal lymph nodes as benign or malignant.

Materials and methods

A total of 70 consecutive patients with mediastinal lymphadenopathy detected on computed tomography (CT) or chest radiograph underwent whole body ¹⁸F-FLT PET/CT and ¹⁸F-FDG PET/CT (within 1 week of each other). Lymph nodal tracer uptake was determined by calculation of standardized uptake value (SUV) with both the tracers. Results of PET/CT were compared with histopathology of the lymph nodes.

Results

Histopathology results showed thirty-seven patients with sarcoidosis, seven patients with tuberculosis, nine patients with non-small cell lung cancer, five patients with Hodgkin’s lymphoma and twelve patients with non-Hodgkin’s lymphoma. The mean FDG SUV_max of sarcoidosis, tuberculosis, Hodgkin’s and non-Hodgkin’s lymphoma was 12.7, 13.4, 8.2, and 8.8, respectively, and the mean FLT SUV_max was 6.0, 5.4, 4.4, and 3.8, respectively. It was not possible to characterize mediastinal lymphadenopathy as benign or malignant solely based on FDG SUV_max values (p > 0.05) or FLT SUV_max values (p > 0.05). There was no significant difference in FDG uptake (p > 0.9) or FLT uptake (p > 0.9) between sarcoidosis and tuberculosis. In lung cancer patients, the FDG SUV_max and FLT SUV_max of those lymph nodes with tumor infiltration on biopsy was 6.7 and 3.9, respectively, and those without nodal infiltration was 6.4 and 3.7, respectively, and both the tracers were not able to characterize the nodal status as malignant or benign (p > 0.05).

Conclusion

Though ¹⁸F-FLT PET/CT and ¹⁸F-FDG PET/CT reflect different aspects of biology, i.e., proliferation and metabolism, respectively, neither tracer could provide satisfactory categorization of benign and malignant lymph nodes. The results of this study clearly suggest that differentiation of mediastinal nodes into benign and malignant solely based on SUV_max values cannot be relied upon, especially in settings where tuberculosis and sarcoidosis are common.

     

18F-FDG PET for the evaluation of thymic epithelial tumors: Correlation with the World Health Organization classification in addition to dual-time-point imaging

Purpose  Our aim was to determine dual-phase ¹⁸F-FDG PET imaging features for various subtypes of thymic epithelial tumors based on the World Health Organization classification. Methods  Forty-six patients with histologically verified thymic epithelial tumors [23 with low-risk tumors (4 with type A, 16 with AB, and 3 with B1) and 23 with high-risk tumors (7 with B2, 5 with B3, and 11 with thymic carcinoma] were enrolled in this study. All patients were injected with ¹⁸F-FDG.; after 1 h, they underwent scanning; after 3 h, 23 patients underwent an additional scanning. The maximum standard uptake value (SUV_max) and the retention index (RI%) of the lesions were determined. Results  The early and delayed SUV_max values in the patients with high-risk tumors [early SUV_max (mean: 6.0) and delayed SUV_max (mean: 7.4)] were both significantly larger than those in patients with low-risk tumors [early SUV_max (mean: 3.2) and delayed SUV_max (mean: 3.4)] (P < 0.05). Early SUV_max values of greater than 7.1 differentiated thymic carcinomas from other types of tumors. For the histological differentiation between high-risk tumors and low-risk tumors, an early SUV_max value of 4.5 was used as the cutoff. The sensitivity, specificity, and accuracy were 78.3, 91.3, and 84.8%, respectively. Conclusion  High SUV values (early SUV > 4.5) suggest the presence of high-risk tumors. A very high SUV value (early SUV > 7.1) is useful for the differentiation of thymic carcinomas from other types of tumors. The delayed SUV values were higher than the early SUV values in all types of tumors.