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1.  FDG-PET/CT imaging for tumor staging and definition of tumor volumes in radiation treatment planning in non-small cell lung cancer 
Oncology Letters  2014;7(4):1015-1020.
18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) has the potential to improve the staging and radiation treatment (RT) planning of various tumor sites. However, from a clinical standpoint, questions remain with regard to what extent PET/CT changes the target volume and whether PET/CT reduces interobserver variability in target volume delineation. The present study analyzed the use of FDG-PET/CT images for staging and evaluated the impact of FDG-PET/CT on the radiotherapy volume delineation compared with CT in patients with non-small cell lung cancer (NSCLC) who were candidates for radiotherapy. Intraobserver variation in delineating tumor volumes was also observed. In total, 23 patients with stage I-III NSCLC were enrolled and treated with fractionated RT-based therapy with or without chemotherapy. FDG-PET/CT scans were acquired within two weeks prior to RT. PET and CT data sets were sent to the treatment planning system, Pinnacle, through compact discs. The CT and PET images were subsequently fused by means of a dedicated RT planning system. Gross tumor volume (GTV) was contoured by four radiation oncologists on CT (GTV-CT) and PET/CT images (GTV-PET/CT). The resulting volumes were analyzed and compared. For the first phase, two radiation oncologists outlined the contours together, achieving a final consensus. Based on PET/CT, changes in tumor-node-metastasis categories occurred in 8/23 cases (35%). Radiation targeting with fused FDG-PET and CT images resulted in alterations in radiation therapy planning in 12/20 patients (60%) in comparison with CT targeting. The most prominent changes in GTV were observed in cases with atelectasis. For the second phase, the variation in delineating tumor volumes was assessed by four observers. The mean ratio of largest to smallest CT-based GTV was 2.31 (range, 1.01–5.96). The addition of the PET results reduced the mean ratio to 1.46 (range, 1.02–2.27). PET/CT fusion images may have a potential impact on tumor staging and treatment planning. Implementing matched PET/CT results reduced observer variation in delineating tumor volumes significantly with respect to CT only.
PMCID: PMC3961455  PMID: 24944661
positron emission tomography/computed tomography; non-small cell lung cancer; radiotherapy; tumor volume
2.  Roles of computed tomography and [18F]fluorodeoxyglucose-positron emission tomography/computed tomography in the characterization of multiple solitary solid lung nodules 
ecancermedicalscience  2012;6:266.
The purpose of this study is to compare the performance of multidetector computed tomography (CT) and positron emission tomography/CT (PET/CT) with [18F]fluorodeoxyglucose in the diagnosis of multiple solitary lung nodules in 14 consecutive patients with suspicious lung cancer. CT and PET/CT findings were reviewed by a radiologist and nuclear medicine physician, respectively, blinded to the pathological diagnoses of lung cancer, considering nodule size, shape, and location (CT) and maximum standardized uptake value normalized to body weight (SUVbw max). Nodules were judged malignant or benign. The sensitivity, specificity, and accuracy of the two techniques were compared. CT had a sensitivity, specificity, and accuracy of 93.7, 86.7, and 90.3%, respectively, whereas PET/CT had a sensitivity, specificity, and accuracy of 75, 100, and 87.1%, respectively. Clinical management would have been erroneous in two patients by CT alone and in four patients by PET/CT alone. In one patient, the two techniques misdiagnosed the nodules (2 CT and 1 PET/CT). CT and PET/CT have complimentary roles in characterization of multiple solitary pulmonary nodules. Small nodules are poorly characterized by CT, and small-sized low-SUV malignant nodules are difficult to detect with PET/CT.
PMCID: PMC3430489  PMID: 22949928
3.  Role of FDG-PET scans in staging, response assessment, and follow-up care for non-small cell lung cancer 
Frontiers in Oncology  2013;2:208.
The integral role of positron-emission tomography (PET) using the glucose analog tracer fluorine-18 fluorodeoxyglucose (FDG) in the staging of non-small cell lung cancer (NSCLC) is well established. Evidence is emerging for the role of PET in response assessment to neoadjuvant therapy, combined-modality therapy, and early detection of recurrence. Here, we review the current literature on these aspects of PET in the management of NSCLC. FDG-PET, particularly integrated 18F-FDG-PET/CT, scans have become a standard test in the staging of local tumor extent, mediastinal lymph node involvement, and distant metastatic disease in NSCLC. 18F-FDG-PET sensitivity is generally superior to computed tomography (CT) scans alone. Local tumor extent and T stage can be more accurately determined with FDG-PET in certain cases, especially in areas of post-obstructive atelectasis or low CT density variation. FDG-PET sensitivity is decreased in tumors <1 cm, at least in part due to respiratory motion. False-negative results can occur in areas of low tumor burden, e.g., small lymph nodes or ground-glass opacities. 18F-FDG-PET-CT nodal staging is more accurate than CT alone, as hilar and mediastinal involvement is often detected first on 18F-FDG-PET scan when CT criteria for malignant involvement are not met. 18F-FDG-PET scans have widely replaced bone scintography for assessing distant metastases, except for the brain, which still warrants dedicated brain imaging. 18F-FDG uptake has also been shown to vary between histologies, with adenocarcinomas generally being less FDG avid than squamous cell carcinomas. 18F-FDG-PET scans are useful to detect recurrences, but are currently not recommended for routine follow-up. Typically, patients are followed with chest CT scans every 3–6 months, using 18F-FDG-PET to evaluate equivocal CT findings. As high 18F-FDG uptake can occur in infectious, inflammatory, and other non-neoplastic conditions, 18F-FDG-PET-positive findings require pathological confirmation in most cases. There is increased interest in the prognostic and predictive role of FDG-PET scans. Studies show that absence of metabolic response to neoadjuvant therapy correlates with poor pathologic response, and a favorable 18F-FDG-PET response appears to be associated with improved survival. Further work is underway to identify subsets of patients that might benefit individualized management based on FDG-PET.
PMCID: PMC3539654  PMID: 23316478
PET; non-small cell lung cancer; staging; response assessment; follow-up
4.  2-Deoxy-2[F-18]FDG-PET for Detection of Recurrent Laryngeal Carcinoma after Radiotherapy: Interobserver Variability in Reporting 
Molecular Imaging and Biology  2008;10(5):294-303.
To evaluate accuracy and interobserver variability in the assessment of 2-deoxy-2[F-18]fluoro-d-glucose-positron emission tomography (FDG-PET) for detection of recurrent laryngeal carcinoma after radiotherapy.
Eleven experienced nuclear physicians from eight centres assessed 30 FDG-PET scans on the appearance of local recurrence (negative/equivocal/positive). Conservative (equivocal analysed as negative) and sensitive (equivocal analysed as positive) assessment strategies were compared to the reference standard (recurrence within 6months after PET).
Seven patients had proven recurrences. For the conservative and sensitive strategy, the mean sensitivity was 87% and 97%, specificity 81% and 63%, positive predictive values 61% and 46% and negative predictive values 96% and 99%, respectively. Interobserver variability showed a reasonable relation in comparison to the reference standard (kappa = 0.55).
FDG-PET has acceptable interobserver agreement and yields good negative predictive value for detection of recurrent laryngeal carcinoma. It could therefore be used as first diagnostic step and may reduce futile invasive diagnostics.
PMCID: PMC2516189  PMID: 18622649
FDG-PET; Laryngeal carcinoma; Radiotherapy; Interobserver variability; Detection; Local recurrence
5.  Prospective use of serial questionnaires to evaluate the therapeutic efficacy of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in suspected lung cancer 
Thorax  2003;58(1):47-51.
Background: A study was undertaken to study the effect of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) on the diagnosis and management of clinically problematic patients with suspected non-small cell lung cancer (NSCLC).
Methods: A prospective before-after study was performed in a cohort of all 164 patients (university/community settings) referred for PET between August 1997 and July 1999. PET was restricted to cases where non-invasive tests had failed to solve clinical problems. The impact on diagnostic understanding and management was assessed using questionnaires (intended treatment without PET, actual treatment choice after PET, post hoc clinical assessment).
Results: Diagnostic problems especially pertained to unclear radiological findings (n=112; 63%), mediastinal staging (n=36; 20%), and distant staging issues (n=16; 9%). PET findings were validated by reviewing medical records. PET had a positive influence on diagnostic understanding in 84%. Improved diagnostic understanding solely based on PET was reported in 26%. According to referring physicians, PET resulted in beneficial change of treatment in 50%. Cancelled surgery was the most frequent change in treatment after PET (35%).
Conclusion: FDG PET applied as "add on" technology in patients with these clinical problems appears to be a clinically useful tool, directly improving treatment choice in 25% of patients. The value of increased confidence induced by PET scanning requires further evaluation.
PMCID: PMC1746467  PMID: 12511720
6.  A pilot study of 4′-[methyl-11C]-thiothymidine PET/CT for detection of regional lymph node metastasis in non-small cell lung cancer 
EJNMMI Research  2014;4:10.
4′-[methyl-11C]-thiothymidine (4DST) is a novel positron emission tomography (PET) tracer to assess proliferation of malignancy. The diagnostic abilities of 4DST and 2-deoxy-2-18 F-fluoro-d-glucose (FDG) for detecting regional lymph node (LN) metastases of non-small cell lung cancer (NSCLC) were prospectively compared. In addition, the relationship between the PET result and the patient's prognosis was evaluated.
A total of 31 patients with NSCLC underwent 4DST PET/computed tomography (CT) and FDG PET/CT. The PET/CT images were evaluated qualitatively and quantitatively for focal uptake of each PET tracer, according to the staging system of the American Joint Committee on Cancer. Surgical and histological results provided the reference standards. Patients were followed for up to two years to assess disease-free survival.
On a per-lesion basis, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for LN staging were 82%, 72%, 32%, 96%, and 73%, respectively, for 4DST, and 29%, 86%, 25%, 88%, and 78%, respectively, for FDG. The sensitivity of 4DST was significantly higher than that of FDG (P < 0.001). The disease-free survival rate with positive 4DST uptake in nodal lesions was 0.35, which was considerably lower than the rate of 0.83 with negative findings (P = 0.04). Among the factors tested, nodal staging by 4DST was the most influential prognostic factor (P = 0.05) in predicting the presence of a previously existing spread lesion or of a recurrence over the course of 2 years.
4DST PET/CT is sensitive for detecting mediastinal lymph node metastasis in NSCLC, but its low specificity is a limitation. However, it may be helpful in predicting the prognosis of NSCLC.
PMCID: PMC3976537  PMID: 24593883
4DST; FDG-PET/CT; Lymph node metastasis; Non-small cell lung cancer (NSCLC); Cell proliferation
7.  Implications of False Negative and False Positive Diagnosis in Lymph Node Staging of NSCLC by Means of 18F-FDG PET/CT 
PLoS ONE  2013;8(10):e78552.
Integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is widely performed in hilar and mediastinal lymph node (HMLN) staging of non-small cell lung cancer (NSCLC). However, the diagnostic efficiency of PET/CT remains controversial. This retrospective study is to evaluate the accuracy of PET/CT and the characteristics of false negatives and false positives to improve specificity and sensitivity.
219 NSCLC patients with systematic lymph node dissection or sampling underwent preoperative PET/CT scan. Nodal uptake with a maximum standardized uptake value (SUVmax) >2.5 was interpreted as PET/CT positive. The results of PET/CT were compared with the histopathological findings. The receiver operating characteristic (ROC) curve was generated to determine the diagnostic efficiency of PET/CT. Univariate and multivariate analysis were conducted to detect risk factors of false negatives and false positives.
The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/ CT in detecting HMLN metastases were 74.2% (49/66), 73.2% (112/153), 54.4% (49/90), 86.8% (112/129), and 73.5% (161/219). The ROC curve had an area under curve (AUC) of 0.791 (95% CI 0.723-0.860). The incidence of false negative HMLN metastases was 13.2% (17 of 129 patients). Factors that are significantly associated with false negatives are: concurrent lung disease or diabetes (p<0.001), non-adenocarcinoma (p<0.001), and SUVmax of primary tumor >4.0 (p=0.009). Postoperatively, 45.5% (41/90) patients were confirmed as false positive cases. The univariate analysis indicated age > 65 years old (p=0.009), well differentiation (p=0.002), and SUVmax of primary tumor ≦4.0 (p=0.007) as risk factors for false positive uptake.
The SUVmax of HMLN is a predictor of malignancy. Lymph node staging using PET/CT is far from equal to pathological staging account of some risk factors. This study may provide some aids to pre-therapy evaluation and decision-making.
PMCID: PMC3808350  PMID: 24205256
8.  On the Added Value of Baseline FDG-PET in Malignant Lymphoma 
Molecular Imaging and Biology  2009;12(2):225-232.
The added value of baseline positron emission tomography (PET) scans in therapy evaluation in malignant lymphoma is unclear. In guidelines, baseline PET is recommended but not mandatory except in lymphoma types with variable fluoro-d-glucose uptake. The aim of the present study was to test the hypothesis that adding baseline PET information decreases false positive readings with posttreatment PET and improves observer agreement.
Forty-four patients (mean age 56 years, standard deviation 14) with malignant lymphoma were included. Two nuclear medicine physicians retrospectively and independently evaluated the posttreatment PET, 3 weeks later followed by paired reading of baseline and posttreatment PET. For each PET, 22 regions were classified as positive, negative, or equivocal, resulting in an overall PET score of positive, unclear, or negative. In case of discrepancies, consensus was reached.
Addition of baseline to posttreatment PET evaluation affected the classification of metabolic response in 34% of malignant lymphoma patients treated with first-line chemotherapy. In one out of seven patients, addition of the baseline PET lead to opposite conclusions (95% confidence interval 4–14). False positivity was reduced by adding the baseline scan information, but the effect on false negativity was similar. In addition, the amount of unclear classifications halved after paired reading. Observer agreement did not improve upon adding the baseline PET data.
Without any other clinical information, pretreatment PET facilitates changes the interpretation of a posttreatment PET in a third of the patients, resulting in both upgrading and downgrading of the posttreatment situation of a malignant lymphoma patient. If these results are confirmed for PET–computed tomography systems, they favor the addition of baseline PET to the current work-up of patients with malignant lymphoma.
PMCID: PMC2844531  PMID: 19809855
FDG PET; Malignant lymphoma; Therapy evaluation; Baseline PET; Hodgkin’s disease; Non-Hodgkin’s lymphoma
9.  Artefacts of PET/CT images 
Positron emission tomography (PET) is a non-invasive imaging modality, which is clinically widely used both for diagnosis and accessing therapy response in oncology, cardiology and neurology.
Fusing PET and CT images in a single dataset would be useful for physicians who could read the functional and the anatomical aspects of a disease in a single shot.
The use of fusion software has been replaced in the last few years by integrated PET/CT systems, which combine a PET and a CT scanner in the same gantry. CT images have the double function to correct PET images for attenuation and can fuse with PET for a better visualization and localization of lesions. The use of CT for attenuation correction yields several advantages in terms of accuracy and patient comfort, but can also introduce several artefacts on PET-corrected images.
PET/CT image artefacts are due primarily to metallic implants, respiratory motion, use of contrast media and image truncation. This paper reviews different types artefacts and their correction methods.
PET/CT improves image quality and image accuracy. However, to avoid possible pitfalls the simultaneous display of both Computed Tomography Attenuation Corrected (CTAC) and non corrected PET images, side by side with CT images is strongly recommended.
PMCID: PMC3097808  PMID: 21614340
PET/CT; artefacts; attenuation correction
10.  Interobserver Variability in Chest CT and Whole Body FDG-PET Screening for Distant Metastases in Head and Neck Cancer Patients 
Molecular Imaging and Biology  2010;13(2):385-390.
The aim of the study was to assess the interobserver variability in chest computed tomography (CT) and whole body 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography (FDG-PET) screening for distant metastases in head and neck squamous cell carcinoma (HNSCC) patients.
Chest CT and whole body FDG-PET of 69 HNSCC patients with high-risk factors who underwent screening for distant metastases were analyzed. All scans were independently read by two experienced radiologists or nuclear physicians who were blinded to the other examinations and follow-up results.
A kappa of 0.516 was found for assessment of size on CT. Kappa values for origin and susceptibility of 0.406 and 0.512 for CT and 0.834 and 0.939 for PET were found, respectively. The overall conclusions had a kappa of 0.517–0.634 for CT and 0.820–1.000 for PET.
In screening for distant metastases in HNSCC patients with high-risk factors, chest CT readings had a reasonable to substantial agreement, while PET readings showed an almost perfect agreement. These findings suggest that for optimal assessment in clinical practice, PET most often can be scored by one observer, but CT should probably more often be scored by different observers in consensus or combined with PET.
PMCID: PMC3051106  PMID: 20533092
CT; FDG-PET; Interobserver agreement; Distant metastases; Head and neck cancer
11.  Lymph node staging in non-small cell lung cancer: evaluation by [18F]FDG positron emission tomography (PET) 
Thorax  1997;52(5):438-441.
BACKGROUND: A study was undertaken to investigate the accuracy of positron emission tomography (PET) with 2-[18F]-fluoro-2-deoxy-D- glucose (FDG) in the thoracic lymph node staging of non-small cell lung cancer (NSCLC). METHODS: Forty six patients with focal pulmonary tumours who underwent preoperative computed tomographic (CT) and FDG- PET scanning were evaluated retrospectively. Thirty two patients had NSCLC and 14 patients had a benign process. The final diagnosis was established by means of histopathological examination at thoracotomy, and the nodal classification in patients with lung cancer was performed by thorough dissection of the mediastinal nodes at surgery. RESULTS: FDG-PET was 80% sensitive, 100% specific, and 87.5% accurate in staging thoracic lymph nodes in patients with NSCLC, whereas CT scanning was 50% sensitive, 75% specific, and 59.4% accurate. The absence of lymph node tumour involvement was identified by FDG-PET in all 12 patients with NO disease compared with nine by CT scanning. Lymph node metastases were correctly detected by FDG-PET in three of five patients with N1 disease compared with two by CT scanning, in nine of 11 with N2 disease compared with six by CT scanning, an in all four with N3 nodes compared with two by CT scanning. CONCLUSIONS: FDG-PET provides a new and effective method for staging thoracic lymph nodes in patients with lung cancer and is superior to CT scanning in the assessment of hilar and mediastinal nodal metastases. With regard to resectability, FDG-PET could differentiate reliably between patients with N1/N2 disease and those with unresectable N3 disease. 

PMCID: PMC1758560  PMID: 9176535
12.  A case of primary lung cancer lesion demonstrated by F-18 FDG positron emission tomography/computed tomography (PET/CT) one year after the detection of metastatic brain tumor 
Oncology Letters  2011;2(4):621-623.
Cancer of unknown primary origin (CUP) is an aggressive disease with a poor prognosis. Metastatic brain tumors occur in approximately 15% of all cancer patients. F-18 2′-deoxy-2fluoro-D-glucose (FDG) positron emission tomography (PET) combined with computed tomography (PET/CT) contributes to the evaluation of cancer staging, although the benefits of PET/CT for detection of CUP origins has yet to be determined. In this study, we present a 37-year-old man with a brain tumor detected by magnetic resonance imaging. Surgical biopsy indicated a metastatic undifferentiated carcinoma, while clinical examination and a CT scan did not detect any abnormalities, with the exception of brain metastases. PET/CT did not reveal abnormal FDG uptake. PET/CT revealed abnormal intense FDG uptake in a small nodular lesion in the right lung 1 year following the detection of brain metastasis, and no other abnormal FDG uptake was observed elsewhere in the body. Right upper lobectomy and dissection of mediastinal lymph nodes were performed. The pathological diagnosis was poorly differentiated adenocarcinoma, which was similar to the brain metastatic lesion, and there was no lymph node metastasis. This case revealed an extremely rare lung cancer with primary lesions demonstrated by PET/CT 1 year after the detection of brain metastasis. This case reveals that F-18 FDG PET/CT imaging of CUP origin is capable of positively impacting on the identification of small primary tumor foci.
PMCID: PMC3406449  PMID: 22848237
PET/CT; metastatic brain tumor; lung cancer; unknown primary origin
13.  Positron emission tomography in ovarian cancer: 18F-deoxy-glucose and 16α-18F-fluoro-17β-estradiol PET 
The most frequently used molecular imaging technique is currently 18F-deoxy-glucose (FDG) positron emission tomography (PET). FDG-PET holds promise in the evaluation of recurrent or residual ovarian cancer when CA125 levels are rising and conventional imaging, such as ultrasound, CT, or MRI, is inconclusive or negative. Recently, integrated PET/CT, in which a full-ring-detector clinical PET scanner and a multidetector helical CT scanner are combined, has enabled the acquisition of both metabolic and anatomic imaging data using one device in a single diagnostic session. This can also provide precise anatomic localization of suspicious areas of increased FDG uptake and rule out false-positive PET findings. FDG-PET/CT is an accurate modality for assessing primary and recurrent ovarian cancer and may affect management. FDG-PET/CT may provide benefits for detection of recurrent of ovarian cancer and improve surgical planning. And FDG-PET has been shown to predict response to neoadjuvant chemotherapy and survival in advanced ovarian cancer. This review focuses on the role of FDG-PET and FDG-PET/CT in the management of patients with ovarian cancer. Recently, we have evaluated 16α-18F-fluoro-17β-estradiol (FES)-PET, which detects estrogen receptors. In a preliminary study we reported that FES-PET provides information useful for assessing ER status in advanced ovarian cancer. This new information may expand treatment choice for such patients.
PMCID: PMC2702339  PMID: 19527525
14.  Influence of Introduction of Positron Emission Tomography on Adherence to Mediastinal Staging Protocols and Performance of Mediastinoscopy 
Journal of Oncology Practice  2007;3(5):242-247.
In this study, we investigated the impact of implementation of [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) in daily practice on adherence to mediastinal staging protocols and performance of mediastinoscopy in non–small-cell lung cancer (NSCLC) patients who are possible candidates for surgical resection. Institutional review board approval was obtained.
Patients and Methods
From a nonuniversity teaching hospital and three surrounding community hospitals in Eindhoven, the Netherlands, we studied data from 143 patients with NSCLC who underwent mediastinoscopy and/or thoracotomy in three consecutive periods (1, 0 to 9 months; 2, 10 to 18 months; and 3, 19 to 31 months) after introduction of PET. Mediastinoscopy was indicated in case of enlarged and/or PET-positive nodes. Adherence to these surgical mediastinal staging guidelines and the performance of PET and mediastinoscopy were investigated and compared between the three periods and with our previous study before introduction of PET.
Results and Conclusion
Guidelines for indicating mediastinoscopy were adequately followed in significantly more instances after introduction of PET (80%), compared with the period before PET (66%). Optimal yield (lymph node stations 4, right and left, and 7) of mediastinoscopy (in 27% of patients) was not significantly different from the period before PET (39% of patients). Compared with the historical data, the percentage of positive mediastinoscopies increased from 15.5 to 17.6 (not significant). We found no significant differences between the three consecutive periods with regard to adequacy of indicating and performance of mediastinoscopy. After introduction of PET, adherence to staging guidelines with respect to mediastinoscopy improved. Although fewer mediastinoscopies had an optimal yield, more proved to be positive for metastases. Nevertheless, when a mediastinoscopy is indicated, surgeons must be encouraged to reach an optimal yield because PET positive nodes might be false negative. This occurred in 5% to 6% of all patients.
PMCID: PMC2793831  PMID: 20859419
15.  A Prospective Analysis of Positron Emission Tomography and Conventional Imaging for Detection of Stage IV Metastatic Melanoma in Patients Undergoing Metastasectomy 
Annals of surgical oncology  2004;11(8):731-738.
Positron emission tomography with 2-deoxy-2-[18F]fluoro-d-glucose (FDG-PET) is available for evaluation of patients with melanoma. This study evaluates the potential of FDG-PET to improve on conventional imaging (CI) in patients with stage IV melanoma undergoing metastasectomy.
This was a prospective study comparing radiological evaluation of patients who underwent metastasectomy for palliation or cure. Patients underwent preoperative evaluation by physical examination, CI by computed tomography and/or magnetic resonance imaging, and FDG-PET. Independent observers performed three separate analyses of CI alone, FDG-PET alone, or FDG-PET read with knowledge of CI (FDG-PET + CI). Abnormalities were reported as benign or malignant and assessed by pathologic analysis or by clinical outcome determined by disease progression detected on serial evaluations.
Ninety-four lesions were noted in 18 patients who underwent preoperative assessment, metastasectomy, and long-term follow up (median, 24 months). Lesion-by-lesion analysis for CI demonstrated a sensitivity of 76%, a specificity of 87%, a positive predictive value (PPV) of 86%, and a negative predictive value (NPV) of 76%. FDG-PET demonstrated a sensitivity of 79%, a specificity of 87%, a PPV of 86%, and an NPV of 80%. For FDG-PET + CI, the sensitivity was 88%, specificity was 91%, and PPV and NPV were 91% and 88%, respectively.
Combined use of FDG-PET and CI may be an accurate strategy to identify sites of disease in patients with stage IV melanoma being considered for metastasectomy. Interpreted independently, FDG-PET and CI seemed to be equivalent modalities. FDG-PET + CI had both the highest sensitivity on lesion-by-lesion analysis and the best accuracy on patient-by-patient analysis.
PMCID: PMC2227906  PMID: 15249335
Melanoma; Cancer; FDG-PET; Imaging; Metastasectomy; Surgery
16.  Quantitative imaging of coronary blood flow 
Nano Reviews  2010;1:10.3402/nano.v1i0.5110.
Positron emission tomography (PET) is a nuclear medicine imaging modality based on the administration of a positron-emitting radiotracer, the imaging of the distribution and kinetics of the tracer, and the interpretation of the physiological events and their meaning with respect to health and disease. PET imaging was introduced in the 1970s and numerous advances in radiotracers and detection systems have enabled this modality to address a wide variety of clinical tasks, such as the detection of cancer, staging of Alzheimer's disease, and assessment of coronary artery disease (CAD). This review provides a description of the logic and the logistics of the processes required for PET imaging and a discussion of its use in guiding the treatment of CAD. Finally, we outline prospects and limitations of nanoparticles as agents for PET imaging.
PMCID: PMC3215216  PMID: 22110860
positron emission tomography (PET); coronary blood flow; myocardial perfusion; quantitative imaging; tissue clearance; blood-tissue exchange model; oxygen-15; ammonia N-13; gamma camera; SPECT
17.  Multifoci Bone Tuberculosis and Lymphadenitis in Mediastinum Mimics Malignancy on FDG-PET/CT: A Case Report 
Positron Emission Tomography with 2-deoxy-[F-18]-fluoro-D-glucose (FDG-PET) has become a reliable diagnostic tool in clinical practice similar to Magnetic Resonance (MR) imaging and Computed Tomography (CT). FDG-PET has especially been used to differentiate malignant from benign lesions, and for staging and follow- up malignant tumors. However, FDG-PET has some pitfalls in cancer screening and FDG tracer accumulates at sites of infection and inflammation. Bone tuberculosis may be confused with malignant tumors of bone and its metastases, and can accumulate focally increased FDG in active period. We present a 60-year-old woman with lytic bone lesions and mediastinal hypermetabolic foci, initially suspected to be malignant by means of FDG-PET and the other imaging modalities; however, bone biopsy confirmed the diagnosis of bone tuberculosis.
Conflict of interest:None declared.
PMCID: PMC3957972  PMID: 24653936
Positron-emission tomography; 18FDG; bone tuberculosis; tumors; diagnosis
18.  The Role of Convex Probe Endobronchial Ultrasound Guided Transbronchial Needle Aspiration in the Diagnosis of Malignant Mediastinal and Hilar Lymph Nodes 
Iranian Journal of Radiology  2012;9(4):183-189.
In the diagnosis of malignant lymph nodes (LNs) and staging of lung cancer, sampling of mediastinal and hilar LNs is essential. Mediastinoscopy is known as the gold standard. Convex probe (CP) endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) is a noninvasive and highly sensitive diagnostic method in mediastinal and hilar LN sampling.
Evaluating the role of CP-EBUS-guided TBNA in the diagnosis of mediastinal and hilar LNs suspicious of malignancy.
Patients and Methods
One hundred twenty patients with a known lung malignancy or hilar/mediastinal LNs detected by thoracic computed tomography (CT) and/or positron emission tomography (PET)-CT suspicious for malignancy were included in this prospective study. The procedure was performed by Olympus 7.5 MHz CP endoscope and EU C2000 processor by the oral route under topical anesthesia and conscious sedation. After visualization of LNs, their dimensions were recorded. Aspiration was considered as “insufficient” if there were inadequate lymphocytes on the smears. Diagnosis of “malignancy” on cytologic examination was considered as the “final diagnosis”. If diagnosis was negative for malignancy, more invasive procedures were performed to confirm the diagnosis.
Twenty four females and 96 male patients (mean age, 57.8 ± 9.1) were included. A total of 177 LN stations were aspirated in 120 patients. In 82 patients, the diagnosis was malignant by EBUS-guided TBNA and in the remaining 38; the diagnosis was established by further invasive procedures. Of the 38 EBUS-guided TBNA negative patients, 28 were diagnosed as non-malignant and 10 were malignant. The sensitivity, diagnostic accuracy and negative predictive value of CP EBUS-guided TBNA were 89.1%, 91.6% and 73.6%, respectively. No major complications were seen.
As an alternative method to mediastinoscopy, EBUS-guided TBNA is a safe and noninvasive procedure with high sensitivity in the diagnosis of malignant mediastinal LNs.
PMCID: PMC3569549  PMID: 23407664
Ultrasonography; Lung Cancer; Mediastinal Neoplasms; Lymph Nodes
19.  Recent developments in PET detector technology 
Physics in medicine and biology  2008;53(17):R287-R317.
Positron emission tomography (PET) is a tool for metabolic imaging that has been utilized since the earliest days of nuclear medicine. A key component of such imaging systems is the detector modules—an area of research and development with a long, rich history. Development of detectors for PET has often seen the migration of technologies, originally developed for high energy physics experiments, into prototype PET detectors. Of the many areas explored, some detector designs go on to be incorporated into prototype scanner systems and a few of these may go on to be seen in commercial scanners. There has been a steady, often very diverse development of prototype detectors, and the pace has accelerated with the increased use of PET in clinical studies (currently driven by PET/CT scanners) and the rapid proliferation of pre-clinical PET scanners for academic and commercial research applications. Most of these efforts are focused on scintillator-based detectors, although various alternatives continue to be considered. For example, wire chambers have been investigated many times over the years and more recently various solid-state devices have appeared in PET detector designs for very high spatial resolution applications. But even with scintillators, there have been a wide variety of designs and solutions investigated as developers search for solutions that offer very high spatial resolution, fast timing, high sensitivity and are yet cost effective. In this review, we will explore some of the recent developments in the quest for better PET detector technology.
PMCID: PMC2891023  PMID: 18695301
20.  Comparison of CT, PET, and PET/CT for Staging of Patients with Indolent Non-Hodgkin’s Lymphoma 
Molecular Imaging and Biology  2009;11(4):269-274.
The aim was to investigate the potential impact of positron emission tomography (PET)/computed tomography (CT) as compared to PET and CT on the staging of patients with indolent lymphoma.
PET/CTs from 45 patients with indolent lymphoma undergoing staging or restaging were studied. Clinical follow-up, additional imaging, and histology served as the gold standard.
PET/CT correctly diagnosed 92 nodal regions as positive for lymphomatous involvement and 458 as disease free vs 68 and 449 for PET and 64 and 459 for CT, respectively. The respective sensitivities, specificities, and accuracies were 99%, 100%, and 99.8% for PET/CT, 68%, 97.5%, and 92.2% for PET, and 70%, 100%, and 94.7% for CT. PET/CT performed significantly better than PET (p < 0.001 for sensitivity, specificity, and accuracy) and CT (p < 0.001 for sensitivity and accuracy). PET/CT also correctly identified significantly more extra-nodal lesions (22) than CT (14) and PET (nine).
PET/CT provides significantly more accurate information compared to PET and CT for the staging and re-staging of patients with indolent lymphoma.
PMCID: PMC2693779  PMID: 19326177
PET; PET/CT; Indolent lymphoma
21.  Experiences and benefits of positron emitted tomography-computed tomography (PET-CT) combined with video-assisted thoracoscopic surgery (VATS) in the diagnosis of Stage 1 sarcoidosis 
Background: The purpose of this study was to describe our experiences and analyze the benefits of video-assisted thoracoscopic surgery (VATS) combined with positron emitted tomography (PET)-computed tomography (CT) in the diagnosis of patients with early (Stage 1) sarcoidosis. Methods: From 1995 to 2006, seven patients (two males, five females), with ages ranging from 26 to 58 years, were impressed with Stage 1 sarcoidosis (mediastinal or hilar lymph nodes involvements without lung involvement) by histological examination of intrathoracic lymph nodes (LNs) and/or lung parenchyma taken from VATS biopsy. Three of them received PET or PET-CT evaluation. VATS was approached from the right and left side in one and six patients, respectively, according to the locations of their lesions. Results: All the VATS biopsied LNs or lung specimens were adequate for establishing diagnosis. Mediastinal LNs were taken from Groups 3, 4 in four, Group 7 in two, and Groups 5, 6 in one of them. Hilar LNs biopsies were performed in four cases. Lung biopsy was performed in all but two cases. All of them were expressed pathologically or radiologically as Stage 1 sarcoidosis. PET-CT revealed high emission signals over these affected LNs. These patients received oral steroid treatment or follow up only. All of them were followed up from 5 months to 11 years with satisfactory results. Conclusion: VATS biopsy is a minimally invasive, safe and effective procedure. It can be used as a diagnostic alternative of transbronchial lung biopsy (TBLB), and can harvest larger and more areas of specimens than mediastinoscopy for staging patients with sarcoidosis. PET-CT can provide us more accurate information about the characteristics and localization of these lesions before biopsy. VATS combined with PET-CT can provide more accurate and earlier diagnosis of patients with unknown intrathoracic lesions, including the sarcoidosis.
PMCID: PMC1879162  PMID: 17565511
Sarcoidosis; Video-assisted thoracoscopic surgery (VATS); Positron emitted tomography-computed tomography (PET-CT)
22.  Challenges and opportunities in patient-specific, motion-managed and PET/CT-guided radiation therapy of lung cancer: review and perspective 
The increasing interest in combined positron emission tomography (PET) and computed tomography (CT) to guide lung cancer radiation therapy planning has been well documented. Motion management strategies during treatment simulation PET/CT imaging and treatment delivery have been proposed to improve the precision and accuracy of radiotherapy. In light of these research advances, why has translation of motion-managed PET/CT to clinical radiotherapy been slow and infrequent? Solutions to this problem are as complex as they are numerous, driven by large inter-patient variability in tumor motion trajectories across a highly heterogeneous population. Such variation dictates a comprehensive and patient-specific incorporation of motion management strategies into PET/CT-guided radiotherapy rather than a one-size-fits-all tactic. This review summarizes challenges and opportunities for clinical translation of advances in PET/CT-guided radiotherapy, as well as in respiratory motion-managed radiotherapy of lung cancer. These two concepts are then integrated into proposed patient-specific workflows that span classification schemes, PET/CT image formation, treatment planning, and adaptive image-guided radiotherapy delivery techniques.
PMCID: PMC3560984  PMID: 23369522
PET; FDG; Respiratory gating; Respiratory tracking; IMRT; IGRT; Adaptive radiotherapy
23.  Managing Lymphoma with Non-FDG Radiotracers: Current Clinical and Preclinical Applications 
BioMed Research International  2013;2013:626910.
Nuclear medicine imaging modalities such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) have played a prominent role in lymphoma management. PET with [18F]Fluoro-2-deoxy-D-glucose (FDG) is the most commonly used tool for lymphoma imaging. However, FDG-PET has several limitations that give the false positive or false negative diagnosis of lymphoma. Therefore, development of new radiotracers with higher sensitivity, specificity, and different uptake mechanism is in great demand in the management of lymphoma. This paper reviews non-FDG radiopharmaceuticals that have been applied for PET and SPECT imaging in patients with different types of lymphoma, with attention to diagnosis, staging, therapy response assessment, and surveillance for disease relapse. In addition, we introduce three radiolabeled anti-CD20 antibodies for radioimmunotherapy, which is another important arm for lymphoma treatment and management. Finally, the relatively promising radiotracers that are currently under preclinical development are also discussed in this paper.
PMCID: PMC3690206  PMID: 23841079
24.  A case of early stage lung cancer detected by repeated cancer screening with positron emission tomography 
Oncology Letters  2011;3(2):297-299.
There has been an increase in the detection rate of small early lung cancer due to recent improvements in imaging technology. However, conventional imaging modalities such as computed tomography (CT) alone are not capable of differentiating small pulmonary nodules. New modalities such as F-18 2′-deoxy-2fluoro-D-glucose (FDG) positron emission tomography combined with CT (PET/CT) have contributed to the evaluation of lung cancer staging, although the differential diagnosis of pulmonary nodules showing ground-glass opacity (GGO) with PET/CT is controversial. In Japan, cancer screening with whole body FDG-PET has been available for asymptomatic individuals, and it has been reported that a wide variety of cancer types are detectable by FDG-PET at potentially curable stages. We present the case of a 62-year-old male with early lung cancer, which was revealed by repeated health screening. A PET/CT scan revealed definite intense FDG uptake (SUVmax 1.2) in the pulmonary nodules of the right upper lobe, while no definite FDG uptake was observed in the lesion in the previous annual screening. Right upper lobectomy was performed, and the pathological diagnosis was well-differentiated adenocarcinoma. Five-year survival has been noted since the thoracotomy, and the patient is doing well without recurrence. This is a significant case of early lung cancer with GGO lesions, which revealed intense FDG uptake during an annual repeated health screening with FDG-PET/CT.
PMCID: PMC3362571  PMID: 22740898
lung cancer; positron emission tomography/computed tomography; screening; ground-glass opacity
25.  Positron Emission Tomography (PET) radiotracers in oncology – utility of 18F-Fluoro-deoxy-glucose (FDG)-PET in the management of patients with non-small-cell lung cancer (NSCLC) 
PET (Positron Emission Tomography) is a nuclear medicine imaging method, frequently used in oncology during the last years. It is a non-invasive technique that provides quantitative in vivo assessment of physiological and biological phenomena. PET has found its application in common practice for the management of various cancers.
Lung cancer is the most common cause of death for cancer in western countries.
This review focuses on radiotracers used for PET scan with particular attention to Non Small Cell Lung Cancer diagnosis, staging, response to treatment and follow-up
PMCID: PMC2579910  PMID: 18928537

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