Fluorine-18 2-deoxy-2-fluoro-D-glucose PET in the preoperative staging of breast cancer: comparison with the standard staging procedures

The present study compared the diagnostic accuracy of fluorine-18 2-deoxy-2-fluoro-D-glucose positron emission tomography (FDG-PET) with conventional staging techniques. The differentiation between malignant and benign lesions and the detection of multifocal disease, axillary and internal lymph node involvement, and distant metastases were evaluated. One hundred and seventeen female patients were prospectively examined using FDG-PET and conventional staging methods such as chest X-ray, ultrasonography of the breast and liver, mammography and bone scintigraphy. All patients were examined on a modern full-ring PET scanner. Histopathological analysis of resected specimens was employed as the reference method. The readers of FDG-PET were blinded to the results of the other imaging methods and to the site of the breast tumour. The sensitivity and specificity of FDG-PET in detecting malignant breast lesions were 93% and 75% respectively. FDG-PET was twofold more sensitive (sensitivity 63%, specificity 95%) in detecting multifocal lesions than the combination of mammography and ultrasonography (sensitivity 32%, specificity 93%). Sensitivity and specificity of FDG-PET in detecting axillary lymph node metastases were 79% and 92% (41% and 96% for clinical evaluation). FDG-PET correctly indicated distant metastases in seven patients. False-positive or false-negative findings were not encountered with FDG-PET. Chest X-ray was false-negative in three of five patients with lung metastases. Bone scintigraphy was false-positive in four patients. Three patients were upstaged since FDG-PET detected distant metastases missed with the standard staging procedure. It is concluded that, compared with the imaging methods currently employed for initial staging, FDG-PET is as accurate in interpreting the primary tumour and more accurate in screening for lymph node metastases and distant metastases. Due to a false-negative rate of 20% in detecting axillary lymph node metastases, FDG-PET cannot replace histological evaluation of axillary status.     

Fluorine-18 fluorodeoxyglucose PET in the preoperative staging of colorectal cancer

Introduction In patients with colorectal cancer (CC), preoperative evaluation and staging should focus on techniques that might alter the preoperative or intraoperative surgical plan. Conventional imaging methods (CT, MRI) have low accuracy for identifying the depth of tumour infiltration and have limited ability to detect regional lymph node involvement. The aim of this study was to evaluate the utility of FDG-PET in the initial staging of patients with CC in comparison with conventional staging methods and to determine its impact on therapeutic management. Methods One hundred and four patients with a diagnosis of CC (53 males and 51 females; mean age 66.76 ± 12.36 years), selected prospectively, were studied for staging using a standard procedure (CT) and FDG-PET. When possible, the reference method was histology. Results In 14 patients, surgery was contraindicated by FDG-PET owing to the extent of disease (only 6/14 suspected by CT). FDG-PET revealed four synchronous tumours. For N staging, both procedures showed a relatively high specificity but a low diagnostic accuracy (PET 56%, CT 60%) and sensitivity (PET 21%, CT 25%). For M assessment, diagnostic accuracy was 92% for FDG-PET and 87% for CT. FDG-PET results led to modification of the therapy approach in 50% of patients with unresectable disease. FDG-PET findings were important, revealing unknown disease in 19.2%, changing the staging in 13.46% and modifying the scope of surgery in 11.54% (with a change in the therapeutic approach in 17.85% of those patients with rectal cancer). Conclusion Compared with conventional techniques, FDG-PET appears to be useful in pre-surgical staging of CC, revealing unsuspected disease and impacting on the treatment approach.     

New high-yield synthesis of 18F-labelled 2-deoxy-2-fluoro-D-glucose

A new high-yield synthesis for the production of 18F-2-FDG has been developed by reacting 18F-labelled acetyl hypofluorite, prepared by in situ reaction of 18F-molecular fluorine with sodium acetate in glacial acetic acid, and tri-acetyl-D-glucal at room temperature. Molecular fluorine labelled with 18F was produced by a 20Ne(d, alpha) 18F reaction. 1,3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-D-glucopyranose is extracted with methylene chloride, evaporated to dryness and hydrolyzed, yielding 98% radiochemically pure 18F-2-FDG. Overall radiochemical yield is about 24 +/- 3%. The specific activity of the final product at the end of synthesis is about 25.38 GBq/mmol (685 mCi/mmol). The synthesis time is approximately 60 min. The synthesis proves that small medical cyclotrons are able to produce 18F-molecular fluorine at the levels needed for the synthesis of 18F-2-FDG used in functional imaging with positron emission tomography.     

18F-FDG PET/CT和CECT预估胃癌术前分期效能的对照研究

胃癌是世界第四大常见的恶性肿瘤[1].尽管外科手术是唯一治愈胃癌的方法·但胃切除术的并发症及致死率较高[2],个体化制订治疗方案可以避免盲目手术带来的严重并发症和致死率[3].而准确的分期可以优化治疗方案、指导外科手术[2].目前,胃癌术前分期没有金标准影像学手段,使用较多的是基于形态学的增强CT(contrast enhancement CT,CECT)检查[妇,但由于其在判断胃早癌等方面的劣势,CECT在术前分期方面不足以完美胜任.近10余年,由于18F-FDG PET/CT可同时提供解剖和代谢信息,可用于病变监测、肿瘤分期以及疗效评估[5],也逐渐被用于胃癌术前分期的预估,但在胃癌术前分期预估中的效能优劣研究结论不尽一致.     

Routine (18)F-FDG PET preoperative staging of colorectal cancer: comparison with conventional staging and its impact on treatment decision making.

The preoperative staging of colorectal cancer (CRC) with (18)F-FDG PET is not as yet generally considered to be evidence based. We have found only 1 study that evaluated (18)F-FDG PET in a nonselected population with proven CRC. Several other studies have concentrated on more advanced disease. The aim of this study was to assess the potential clinical benefit of (18)F-FDG PET in the routine staging of CRC. METHODS: Thirty-eight consecutive patients who had had CRC histologically proven by colonoscopy underwent prospective preoperative staging by plain chest radiography, sonography, CT, and (18)F-FDG PET. Sensitivity, specificity, and accuracy were retrospectively assessed by comparison with the histologic results after surgery (36 patients) or clinical follow-up (2 inoperable cases-both patients died within 1 y of the PET examination). The impact of (18)F-FDG PET on therapeutic decision making was evaluated by comparing medical records before and after (18)F-FDG PET. RESULTS: (18)F-FDG PET correctly detected 95% of primary tumors, whereas CT and sonography correctly detected only 49% and 14%, respectively. Lymph nodes were involved in 7 patients. The sensitivity, specificity, and accuracy of (18)F-FDG PET were 29%, 88%, and 75%, respectively. CT and sonography did not reveal any lymph node involvement. Liver metastases were present in 9 patients. (18)F-FDG PET, CT, and sonography had a sensitivity of 78%, 67%, and 25%, respectively; a specificity of 96%, 100%, and 100%, respectively; and an accuracy of 91%, 91%, and 81%, respectively. (18)F-FDG PET revealed further lesions in 11 patients. Levels of carcinoembryonic antigen and carbohydrate antigen 19-9 tumor markers were elevated in, respectively, only 33% and 8% of cases of proven CRC. (18)F-FDG PET changed the treatment modality for 8% and the range of surgery for 13% of patients. In total, (18)F-FDG PET changed the method of treatment for 16% of patients. CONCLUSION: Plain chest radiography and sonography did not bring any clinical benefits. No correlation was found between the level of tumor markers and the stage of disease. CT is necessary for confirmation of PET findings at extraabdominal sites (PET-guided CT) and for their morphologic specification at abdominal and pelvic sites before an operation. (18)F-FDG PET is the best method for the staging of CRC in all localities, despite the high rate of false-negative PET findings in patients with lymph node involvement. PET should be performed as a first examination after verification of CRC. We propose a PET/CT hybrid system as optimal in the staging of CRC.     

Impact of FDG PET on the preoperative staging of newly diagnosed breast cancer

Purpose The main objective of this study was to determine the efficacy of ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG PET) to assess the impact of this technique in staging of patients with newly diagnosed breast cancer. Methods Two hundred and seventy-one consecutive patients (median age = 51 ± 11 years) with biopsy-proven primary breast cancer who were examined by FDG PET were enrolled in this prospective preoperative staging study. Whole-body FDG-PET images were acquired approximately 60 min after the intravenous administration of FDG (5.2 MBq/kg). Visual assessment and the maximum standardized uptake value (SUVmax) of breast lesions for semiquantitative analysis were carried out. The PET results were compared with the histopathology results. Results For the tumor, node, metastases (TNM) staging, 240 patients (250 breasts) were considered eligible based on the criteria that were established for this analysis. Significant differences were noted in SUVmax of lesions according to the TNM staging (p < 0.05). The average SUVmax of the primary tumor was calculated in patients with axillary involvement (n = 58) and for the ones without axillary metastasis (n = 79), and SUVmax were 4.1 ± 3.5 and 2.8 ± 2.3, respectively, with a significant difference between the two groups (p = 0.03). PET imaging revealed pathological FDG uptake in 54% (46/85) of patients with axillary lymph node metastases. The sensitivities of FDG PET for detecting axillary lymph node metastasis were found 41% in pN1, 67% in pN2, and 100% in pN3, and the specificity was 89% for pN0 stage. Detection of extra-axillary regional node or distant metastatic lesions revealed by PET scan in 22 of 24 patients resulted in a significant change in the TNM stage. Distant metastasis without axillary lymph node metastasis was noted in 21% (5/24) of patients. The results revealed that FDG PET upgraded TNM stage in 9.2% (22/240) of patients and 7.5% (18/240) of patients were diagnosed as having one or more distant metastases. Conclusion FDG PET was able to identify extra-axillary regional nodal and distant lesions in newly diagnosed patients with breast cancer; FDG PET may alter the staging and management of therapy in patients with newly diagnosed breast cancer.     

18F-FDG PET for staging breast cancer in patients with inner-quadrant versus outer-quadrant tumors: comparison with long-term clinical outcome.

Extraaxillary metastases (i.e., in the absence of axillary involvement) are more likely to develop in patients with inner-quadrant (IQ) breast cancer than in patients with outer-quadrant (OQ) primary tumors. The relative difficulty of identifying extraaxillary metastases may lead to understaging of cancer in these patients. This study examined whether (18)F-FDG PET findings were differentially associated with the location of primary tumors, and with long-term prognosis, in IQ and OQ patients. METHODS: Follow-up data were obtained for 141 patients whose breast cancer was staged by PET and who were documented to have IQ (n = 42) or OQ (n = 99) primaries. Results were stratified according to PET findings consistent with different metastatic patterns. Data were further analyzed with respect to disease outcome after a mean 3-y follow-up period. RESULTS: Among IQ patients, progressive disease was identified in 26.1%, compared with 13.1% of OQ patients, for a relative risk (RR) of 2.0. Of patients with PET findings of isolated extraaxillary metastases, 36.1% had progressive disease, compared with 10.7% of other patients (RR = 3.4), and 61.9% of IQ patients had isolated extraaxillary metastases identified on PET, compared with 10.1% of OQ patients (RR = 6.1). CONCLUSION: IQ patients demonstrated a 6-fold greater frequency of PET findings of isolated extraaxillary metastasis, and such findings were associated with triple the risk for disease progression. Patients with IQ tumors could be vulnerable to understaging with conventional staging approaches and may particularly benefit from PET during the staging process.     

Integrated PET/CT in the preoperative staging of lung cancer: A prospective comparison of CT,PET and integrated PET/CT

Purpose

The purpose of this study was to evaluate the role of integrated PET/CT in the staging of lung cancer compared with CT alone or PET alone.

Materials and methods

Thirty-three patients underwent integrated PET/CT for the staging of lung cancer. The tumor, node and metastasis (TNM) stages were assessed with CT, PET and integrated PET–CT and compared with the surgical and pathological staging.

Results

CT correctly evaluated the (T) status in (64%) of the patients, PET in (59%) and PET/CT in (86%). CT correctly evaluated the (N) status in (73%) of the patients, PET in (76%), and PET/CT (88%) with accuracy, sensitivity, specificity, PPV and NPV were 73%, 78%, 71%, 50% and 94% for CT, 76%, 67%, 79%, 55% and 95% for PET and 88%, 89%, 88%, 73% and 100% for PET/CT respectively, and for (M) status were 91%, 86%, 92%, 75% and 96% for CT, 88%, 71%, 92%, 71% and 92% for PET and 97%, 100%, 96%, 88% and 100% for PET/CT respectively. Regarding the overall TNM staging CT correctly staged 24 patients. PET correctly staged 23 cases while PET/CT correctly staged 30 cases. A significant difference in the accuracy of overall tumor staging between PET/CT and CT (P = 0.0412) or PET (P = 0.0233).

Conclusion

The integrated PET/CT is superior to either CT or PET in the staging of lung cancer which has an important impact on selection of the appropriate treatment regimen.     

Role of ultrasound in the preoperative staging of patients with breast cancer

The aim of this study was to evaluate the ability of axillary ultrasound (US) and US-guided fine-needle aspiration biopsy (FNAB) to detect axillary LN metastases. Between January 2001 and September 2003, axillary US was performed in 165 patients with cytologically or histologically proven breast cancer and clinically non-palpable axillary LNs. In patients with US suspicious LNs, US-guided FNAB was performed and patients with cytologically proven malignant LNs proceeded directly to the ALND. In 49/90 patients with US suspicious LNs, US-guided FNAB was performed. It was positive in 33/49 patients. Definitive histology report revealed LN metastases in 65/165 patients. The sensitivity, specificity, positive and negative predictive value of the US-FNAB, were 84, 91, 97 and 62%. Axillary US in a combination with US-FNAB is a valuable method in preoperative staging of patients with breast cancer. Almost 50% of patients with LN metastases can be spared the second operation. However, it is very much operator-dependent and equipment-dependent.     

Gamma-camera 18F-FDG PET in diagnosis and staging of patients presenting with suspected lung cancer and comparison with dedicated PET.

It is not clear whether high-quality coincidence gamma-PET (gPET) cameras can provide clinical data comparable with data obtained with dedicated PET (dPET) cameras in the primary diagnostic work-up of patients with suspected lung cancer. This study focuses on 2 main issues: direct comparison between foci resolved with the 2 different PET scanners and the diagnostic accuracy compared with final diagnosis determined by the combined information from all other investigations and clinical follow-up. METHODS: Eighty-six patients were recruited to this study through a routine diagnostic program. They all had changes on their chest radiographs, suggesting malignant lung tumor. In addition to the standard diagnostic program, each patient had 2 PET scans that were performed on the same day. After administration of 419 MBq (range = 305-547 MBq) (18)F-FDG, patients were scanned in a dedicated PET scanner about 1 h after FDG administration and in a dual-head coincidence gamma-camera about 3 h after tracer injection. Images from the 2 scans were evaluated in a blinded set-up and compared with the final outcome. RESULTS: Malignant intrathoracic disease was found in 52 patients, and 47 patients had primary lung cancers. dPET detected all patients as having malignancies (sensitivity, 100%; specificity, 50%), whereas gPET missed one patient (sensitivity, 98%; specificity, 56%). For evaluating regional lymph node involvement, sensitivity and specificity rates were 78% and 84% for dPET and 61% and 90% for gPET, respectively. When comparing the 2 PET techniques with clinical tumor stage (TNM), full agreement was obtained in 64% of the patients (Cohen's kappa = 0.56). Comparing categorization of the patients into clinical relevant stages (no malignancy/malignancy suitable for treatment with curative intent/nontreatable malignancy), resulted in full agreement in 81% (Cohen's kappa = 0.71) of patients. CONCLUSION: Comparing results from a recent generation of gPET cameras obtained about 2 h later than those of dPET, there was a fairly good agreement with regard to detecting primary lung tumors but slightly reduced sensitivity in detecting smaller malignant lesions such as lymph nodes. Depending on the population to be investigated, and if dPET is not available, gPET might provide significant diagnostic information in patients in whom lung cancer is suspected.     

18F-FLT PET for visualization of laryngeal cancer: comparison with 18F-FDG PET.

The feasibility of (18)F-3'-fluoro-3'-deoxy-L-thymidine PET (FLT PET) for detecting laryngeal cancer was investigated and compared with (18)F-FDG PET. METHODS: Eleven patients diagnosed with or strongly suspected of having recurrent laryngeal cancer and 10 patients with histologically proven primary laryngeal cancer underwent attenuation-corrected (18)F-FLT PET imaging 60 min after injection of a median of 213 MBq (range, 175-400 MBq) (18)F-FLT and attenuation-corrected (18)F-FDG PET imaging 90 min after injection of a median of 340 MBq (range, 165-650 MBq) (18)F-FDG. All patients were staged by endoscopy and CT according to the Union Internationale Contre la Cancer TNM staging system. All patients underwent biopsy of the laryngeal area after imaging. Lesions seen on (18)F-FDG PET and (18)F-FLT PET were compared with histopathologic results. Mean SUVs, maximum SUVs, and tumor-to-nontumor (TNT) ratios were calculated for (18)F-FLT and (18)F-FDG. Wilcoxon nonparametric testing was used for comparison of (18)F-FDG with (18)F-FLT uptake. The Spearman correlation coefficient was used to correlate mean SUVs, maximum SUVs, and TNT ratios of (18)F-FDG PET and (18)F-FLT PET. Two-tailed P values < 0.05 were considered significant. RESULTS: (18)F-FDG PET and (18)F-FLT PET detected laryngeal cancer correctly in 15 of 17 patients. One lesion judged as positive on (18)F-FDG PET turned out to be normal tissue. Of 2 lesions judged as positive on (18)F-FLT PET, 1 turned out to be inflammation and the other to be normal tissue. Maximum SUVs were 3.3 (range, 1.9-8.5) for (18)F-FDG and 1.6 (range, 1.0-5.7) for (18)F-FLT (P < 0.001). Mean SUVs were 2.7 (range, 1.5-6.5) for (18)F-FDG and 1.2 (range, 0.8-3.8) for (18)F-FLT (P < 0.001). TNT was 1.9 (range, 1.3-4.7) for (18)F-FDG and 1.5 (range, 1.1-3.5) for (18)F-FLT (P < 0.05). CONCLUSION: The numbers of laryngeal cancers detected with (18)F-FLT PET and (18)F-FDG PET were equal. In laryngeal cancer, the uptake of (18)F-FDG is higher than that of (18)F-FLT.     

Non-small cell lung cancer: dual-modality PET/CT in preoperative staging

PURPOSE: To determine the accuracy of dual-modality positron emission tomographic (PET)-computed tomographic (CT) imaging, as compared with PET alone and CT alone, in the staging of non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Twenty-seven patients with NSCLC underwent staging with combined fluorine 18 fluorodeoxyglucose PET and CT. CT, PET, and coregistered PET/CT images were evaluated separately by two different physicians for each imaging modality, and disease stage was determined by using TNM and American Joint Committee on Cancer staging systems. Histopathologic results served as the reference standard. The statistical significance of differences among CT, PET, and PET/CT was determined by using the McNemar test. RESULTS: Overall tumor stage was correctly classified as 0-IV with CT in 19 patients, with PET in 20 patients, and with PET/CT in 26 patients. PET/CT findings when compared with PET findings led to a treatment change for four patients (15%) and when compared with CT findings led to a treatment change for five patients (19%). Differences in the accuracy of overall tumor staging between PET/CT and CT (P =.008) and between PET/CT and PET (P =.031) were significant. Primary tumor stage was correctly determined in more patients with PET/CT than with either PET alone or CT alone. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of regional lymph node staging, respectively, were 89%, 94%, 89%, 94%, and 93%, with PET/CT; 89%, 89%, 80%, 94%, and 89% with PET; and 70%, 59%, 50%, 77%, and 63% with CT. Fourteen distant metastases were detected in four patients with CT, four were detected in two patients with PET, and 17 were detected in four patients with PET/CT. CONCLUSION: Use of dual-modality PET/CT significantly increases the number of patients with correctly staged NSCLC and thus has a positive effect on treatment.     

Rapid, inexpensive quality control of fluorine-18 2-deoxy-2-fluoro-D-glucose preparations using the hexokinase reaction in vitro

A rapid enzymatic method for determining the purity of 2FDG preparations has been devised. A small aliquot of the preparation is incubated with a hexokinase/adenosine triphosphate/Mg+2 mixture and passed through a Dowex 1 ion-exchange column, which retains the 2FDG-6-phosphate. Another aliquot, without prior incubation, is passed through an identical column and the 2FDG radioactivity is found in the eluant. The criteria for purity are quantitative retention of the 2FDG-6-phosphate on the column and no retention of 2FDG. Comparison of the HK method with thin layer and high performance liquid chromatography assays indicate that the HK method can serve as a rapid, simple and inexpensive alternative to these other methods. It can be used in a routine quality control program and may be easily adaptable to automated 2FDG synthetic methods.     

Impact of whole-body 18F-FDG PET on staging and managing patients with breast cancer: the referring physician's perspective.

FDG PET has emerged as an important clinical imaging modality for diagnosing and staging cancer. However, the impact of FDG PET on staging and managing patients with breast cancer from the referring physician's point of view is unknown. METHODS: The referring physicians of 160 breast cancer patients received standardized questionnaires inquiring if and how PET findings altered their patient's stage and their clinical management decisions. Management changes were classified as intermodality if the change was from one modality to another (e.g., medical to surgical, surgical to radiation, medical to no treatment, and vice versa) or as intramodality if the change was within the same modality (e.g., altered medical or radiotherapy approach). RESULTS: Fifty of the 160 surveys were completed (31% response rate). PET changed the clinical stage in 36% of patients (28% upstaged, 8% downstaged) and resulted in intermodality changes in 28% of patients and intramodality changes in 30% of patients. CONCLUSION: The results of this prospective survey show that FDG PET has a major impact on the management of breast cancer patients, influencing both clinical stage and management in more than 30% of patients.     

Consistency and prognostic value of preoperative staging and postoperative pathological staging using 18 F-FDG PET/MRI in patients with non-small cell lung cancer

Annals of Nuclear Medicine - In recent years, positron emission tomography/magnetic resonance imaging (PET/MRI) has been clinically used as a method to diagnose non-small cell lung cancer (NSCLC)....