Lutz S. Freudenberg

Accuracy of Whole-Body Dual-Modality Fluorine-18–2-Fluoro-2-Deoxy-d-Glucose Positron Emission Tomography and Computed Tomography (FDG-PET/CT) for Tumor Staging in Solid Tumors: Comparison With CT and PET

PURPOSE To assess the accuracy of positron emission tomography/computed tomography (PET/CT) when staging different malignant diseases. PATIENTS AND METHODS This was a retrospective, blinded, investigator-initiated study of 260 patients with various oncological diseases who underwent fluorine-18-2-fluoro-2-deoxy-d-glucose PET/CT for tumor staging. CT images alone, PET images alone, PET + CT data viewed side by side, and fused PET/CT images were evaluated separately according to the tumor-node-metastasis system. One hundred forty patients with tumors not staged according to the tumor-node-metastasis system or a lack of reference standard were excluded from data analysis; 260 patients were included. Diagnostic accuracies were determined for each of the four image sets. Histopathology and a clinical follow-up of 311 (+/- 125) days served as standards of reference. RESULTS PET/CT proved significantly more accurate in assessing tumor-node-metastasis system stage compared with CT alone, PET alone, and side-by-side PET + CT (P < .0001). Of 260 patients, 218 (84%; 95% CI, 79% to 88%) were correctly staged with PET/CT, 197 (76%; 95% CI, 70% to 81%) with side-by-side PET + CT, 163 (63%; 95% CI, 57% to 69%) with CT alone, and 166 (64%; 95% CI, 58% to 70%) with PET alone. Combined PET/CT had an impact on the treatment plan in 16, 39, and 43 patients when compared with PET + CT, CT alone, and PET alone, respectively. CONCLUSION Tumor staging with PET/CT is significantly more accurate than CT alone, PET alone, and side-by-side PET + CT. This diagnostic advantage translates into treatment plan changes in a substantial number of patients.

FDG-PET/CT in re-staging of patients with lymphoma

The aim of this study was to evaluate the clinical significance of combined fluorine-18 fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) in patients with lymphoma, and to compare the FDG-PET/CT staging results with those of FDG-PET and CT alone. Twenty-seven patients were studied. Each patient had clinical follow-up for >12 months and entered complete follow-up evaluation. Patient-based evaluation showed a sensitivity of 78% for CT alone, 86% for FDG-PET alone, 93% for CT and FDG-PET read side by side, and 93% for combined FDG-PET/CT imaging. Region-based evaluation showed a sensitivity for regional lymph node involvement of 61%, 78%, 91% and 96% respectively. FDG-PET/CT imaging is superior to CT alone (P=0.02) and has additional benefit over FDG-PET alone due to exact anatomical localisation. We conclude that FDG-PET/CT imaging is accurate in re-staging lymphoma and offers advantages over separate FDG-PET and CT imaging.

Hybrid Imaging by SPECT/CT and PET/CT: Proven Outcomes in Cancer Imaging

The last decade has seen the development of hybrid imaging technologies combining positron emission tomography (PET) or single-photon emission computed tomography (SPECT) with x-ray computed tomography (CT). Numerous studies demonstrate the superiority of PET/CT and SPECT/CT over stand-alone PET and SPECT in terms of diagnostic accuracy. For PET with (18)F-fluorodeoxyglucose (FDG), this has been demonstrated for bronchial carcinomas, high-grade lymphomas, melanomas, and head and neck tumors, to name a few. Combined imaging of structure and biochemistry is expected to be even more important for tracers such as (124)I that are more specific for tumor tissue. Similarly, SPECT/CT has revolutionized the field of conventional nuclear medicine. Available evidence indicates that this hybrid imaging technology will become the gold standard for conventional scintigraphy, including bone imaging performed for staging malignancy, and also for the so-called tumor scintigraphies that visualize neoplastic foci via tumor-specific agents such as octreotide labeled with (111)In or (131)I. Another important indication for SPECT/CT is sentinel lymph node scintigraphy, where SPECT/CT fusion helps considerably in localizing the first lymph node draining a tumor. Technological progress never stands still; hybrid cameras combining PET and MRI have already been introduced. These systems will lead medical imaging to new horizons, and they will offer the virtually unlimited potential of simultaneously acquiring morphologic, functional, and molecular information about the living human body.

Value of 124I-PET/CT in staging of patients with differentiated thyroid cancer

The aim of this study is to evaluate the clinical significance of 124I positron emission tomography (PET) using a combined PET/CT tomograph in patients with differentiated thyroid carcinoma and to compare the PET/CT results with 131I whole-body scintigraphy (WBS), dedicated PET and CT alone. Twelve thyroid cancer patients were referred for diagnostic workup and entered complete clinical evaluation, including histology, cytology, thyroglobulin level, ultrasonography, fluorine-18 fluorodeoxyglucose (FDG)-PET, FDG-PET/CT and CT. Lesion-based evaluation showed a lesion delectability of 56, 87 and 100% for CT, 124I-PET, and combined 124I-PET/CT imaging, respectively. Lesion delectability of 131I-WBS was 83%. We conclude that 124I-PET/CT imaging is a promising technique to improve treatment planning in thyroid cancer. It is particularly valuable in patients suffering from advanced differentiated thyroid cancer prior to radio-iodine therapy and in patients with suspected recurrence and potential metastatic disease.

Variations in Clinical PET/CT Operations: Results of an International Survey of Active PET/CT Users

This study gathered information about clinical PET/CT operations worldwide to help guide discussions on the use and standardization of clinical PET/CT. Methods: A Web-based survey of PET/CT users was initiated in November 2009 through e-mail advertising using Academy of Molecular Imaging databases. Recipients were asked 58 questions related to demographics (e.g., location, number of PET/CT systems, and staffing), PET/CT operations and use, and variations in 18F-FDG oncology imaging protocols. Results: The responders were from centers in the Americas (71%), Europe (22%), Asia-Pacific (6%), and Middle East (1%), with most responding sites representing public health care institutions (60%). PET/CT systems were most frequently installed in nuclear medicine departments (59%). Of the sites operating a PET/CT system, 16% had 10 y or more of stand-alone PET experience. About 40% of all sites operated at least 2 PET/CT systems. PET/CT was most frequently used for applications in torso or whole-body oncology (87%), radiation therapy planning (4%), cardiology (4%), and neurology (5%). The average interval of fasting before an 18F-FDG PET/CT examination was 7 ± 3 h (range, 4–12 h). Blood glucose levels were measured at 99% of sites, but acceptable maximal glucose levels varied substantially (an upper limit of 200 mg/dL was applied at >50% of the institutions). A weight-based radioactivity dose injection was performed at 44% of sites. The mean 18F-FDG activity injected was 390 MBq (range, 110–585 MBq) for 3-dimensional PET of a 75-kg patient. The mean uptake time was 64 ± 14 min (range, 20–90 min). Split protocols involving patient repositioning and adapted imaging parameters were used at 51% of sites. Only 41% used patient positioning aids. Intravenous or oral CT contrast material was used at 52% of sites in up to 25% of patients. Most sites (90%) measured maximum standardized uptake value as an index of tissue glucose use. Only 62% of sites provided a fully integrated PET/CT report. Conclusion: An international survey among clinical PET/CT users revealed significant variations in standard 18F-FDG PET/CT protocols. This finding illustrates the need for continuous training and ongoing standardization in an effort to optimize PET/CT in oncology.

Breast Cancer Staging in a Single Session: Whole-Body PET/CT Mammography

Our objective was to compare the diagnostic accuracy of an all-in-one protocol of whole-body 18F-FDG PET/CT and integrated 18F-FDG PET/CT mammography with the diagnostic accuracy of a multimodality algorithm for initial breast cancer staging. Methods: Forty women (mean age, 58.3 y; range, 30.8–78.4 y; SD, 12 y) with suspected breast cancer were included. For the primary tumor, we compared 18F-FDG PET/CT mammography versus MRI mammography; for axillary lymph node status, 18F-FDG PET/CT versus clinical investigation and ultrasound; and for distant metastases, 18F-FDG PET/CT versus a multimodality staging algorithm. Histopathology and clinical follow-up served as the standard of reference. The Fisher exact test evaluated the significance of differences (P < 0.05). Alterations in patient management caused by 18F-FDG PET/CT were documented. Results: No significant differences were found in the detection rate of breast cancer lesions (18F-FDG PET/CT, 95%; MRI, 100%; P = 1). 18F-FDG PET/CT correctly classified lesion focality significantly more often than did MRI (18F-FDG PET/CT, 79%; MRI, 73%; P < 0.001). MRI correctly defined the T stage significantly more often than did 18F-FDG PET/CT (MRI, 77%; 18F-FDG PET/CT, 54%; P = 0.001). 18F-FDG PET/CT detected axillary lymph node metastases in 80% of cases; clinical investigation/ultrasound, in 70%. This difference was not statistically significant (P = 0.067). Distant metastases were detected with 18F-FDG PET/CT in 100% of cases, and the multimodality algorithm identified distant metastases in 70%. This difference was not statistically significant (P = 1). Three patients had extraaxillary lymph node metastases that were detected only by PET/CT (cervical, retroperitoneal, mediastinal/internal mammary group). 18F-FDG PET/CT changed patient management in 12.5% of cases. Conclusion: Our data suggest that a whole-body 18F-FDG PET/CT mammography protocol may be used for staging breast cancer in a single session. This initial assessment of the 18F-FDG PET/CT protocol indicates similar accuracy to MRI for the detection of breast cancer lesions. Although MRI seems to be more accurate when assessing the T stage of the tumor, 18F-FDG PET/CT seems able to more accurately define lesion focality. Although 18F-FDG PET/CT mammography was able to detect axillary lymph node metastases with a high sensitivity, this method cannot soon be expected to replace the combination of clinical examination, ultrasound, and sentinel lymph node biopsy for axillary assessment.

Optimized 124I PET Dosimetry Protocol for Radioiodine Therapy of Differentiated Thyroid Cancer

Iodine kinetics and lesion dose per administered 131I activity (LDpA) of differentiated thyroid cancer metastases were determined using 124I PET. These data were analyzed to derive an optimized dosimetry protocol. Methods: We evaluated the time-activity-concentration curves of 37 lesions in 17 patients who had undergone thyroidectomies. LDpA determination involved 124I PET images acquired at 4, 24, 48, 72, and 96 h after intake of a capsule containing 20–40 MBq of 124I. A combination of a linear and a monoexponential or a monoexponential function only parameterized the time-activity-concentration curves. The LDpAs, calculated using data from all 5 PET time points, served as reference. The lesions were classified into 3 groups, according to potential for cure with 131I therapy: low (≤5 Gy GBq−1; n = 14), medium (between 5 and 10 Gy GBq−1; n = 9), or high LDpAs (>10 Gy GBq−1; n = 14). Using the reference approach, the differences in the empiric kinetic parameters within the LDpA groups were evaluated. The reference LDpAs were compared with those derived from only 2, 3, or 4 PET data points and from 1 adapted 2-point approach. Lins concordance correlation coefficient (ρc) and the mean absolute percentage deviation in LDpAs were used to assess agreement between simplified and reference approaches. Results: The effective 124I half-life, linear activity–concentration rate (α), and 24-h activity concentration (CpA) (the latter 2 per administered 124I activity) differed significantly among the LDpA groups (P < 0.05). LDpAs correlated with 24-h CpAs (r = 0.94, P < 0.001). Using the 4-, 24-, and 96-h measurements, a ρc value of greater than or equal to 0.90 was found, and the mean absolute percentage deviation was less than or equal to 16%. Similar statistical values were obtained for the adapted approach, which was based on 24- and 96-h PET data points only. Conclusion: Lesion classification into LDpA groups was feasible using a single PET scan at ∼24 h. Because of the highly variable kinetics, 1 additional measurement at ∼96 h was needed to obtain a sufficiently reliable LDpA estimate. The adapted 24-96-h approach appears to be the optimal 124I protocol and is a reliable simplification of the 5-point protocol.

Dual Modality of 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography in Patients with Cervical Carcinoma of Unknown Primary

Objective: To evaluate an optimized F-18-flurodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) acquisition protocol for head and neck cancer and assess the usefulness of combined FDG-PET/CT in locating unknown primary tumors in patients with biopsy-proven cervical lymph node metastases. Subjects and Methods: Twenty-one patients with cervical lymph node metastases of unknown primary tumors underwent staging with FDG-PET/CT. The images of FDG-PET alone, CT alone, FDG-PET/CT read side by side and fused and FDG-PET/CT were evaluated separately by 2 physicians. Imaging results were correlated with either histology (n = 14) or clinical follow-up (n = 7). Results: On the fused FDG-PET/CT images, primary tumors were identified in 12 patients (57%); with FDG-PET alone and FDG-PET and CT read side by side 11 (52%) primary tumors were found while CT alone identified 5 (23%) primary tumors. Conclusion: Our data indicate that fused FDG-PET and CT images increased the sensitivity of detecting carcinoma of unknown primary (CUP) tumors compared to CT alone, but not to FDG-PET alone or FDG-PET and CT read side by side. Hence accurate fusion of functional and morphologic data by FDG-PET/CT is a promising imaging modality in the clinical workup of patients with cervical CUP tumors.

Morphologic and Functional Changes in Nontumorous Liver Tissue After Radiofrequency Ablation in an In Vivo Model: Comparison of 18F-FDG PET/CT, MRI, Ultrasound, and CT

Rimlike contrast enhancement on morphologic imaging and increased tracer uptake on 18F-FDG PET in the periphery of the necrosis can hamper differentiation of residual tumor from regenerative tissue after radiofrequency ablation of liver lesions. This study used MRI, CT, ultrasound, and 18F-FDG PET/CT to assess the typical appearance of lesions in nontumorous animal liver tissue after radiofrequency ablation. Methods: Lesions were created by radiofrequency ablation of normal liver parenchyma in 21 minipigs. Follow-up was performed by 3 contrast-enhanced morphologic modalities—MRI, CT, and ultrasound—and by 18F-FDG PET/CT immediately, 3 and 10 d, and 1, 2, 3, and 6 mo after radiofrequency ablation. Images were evaluated qualitatively for areas of increased enhancement and regions of elevated tracer uptake. Furthermore, all images were assessed quantitatively by determination of ratios comparing enhancement/tracer uptake in the periphery of the necrosis with enhancement/tracer uptake in normal liver parenchyma. Imaging findings were compared with histopathology findings. Results: Immediately after radiofrequency ablation, no increase in 18F-FDG uptake was visible, whereas elevated enhancement was noticed in the periphery of the necrosis on all morphologic imaging procedures. At further follow-up, an area of rimlike increase in 18F-FDG uptake surrounding the necrosis was detected on PET/CT. The rimlike pattern of increased enhancement in the arterial phase was present for all liver lesions on CT, MRI, and ultrasound, especially between day 3 and month 1 after the radiofrequency ablation. Both elevated glucose metabolism and enhancement persisted for 6 mo postinterventionally. Histologic examination showed a hemorrhagic border converting into a regeneration capsule. Conclusion: If performed immediately after radiofrequency ablation, 18F-FDG PET/CT probably has benefits over those of morphologic imaging procedures when assessing liver tissue for residual tumor. Later follow-up may be hampered by visualization of peripheral hyperperfusion and tissue regeneration. Further studies on a patient population are essential.

Subjective Perception of Radiation Risk

Physicians, medical staff, and patients, much like the general population, are becoming increasingly sensitized to the issue of radiation exposure from diagnostic or therapeutic procedures. The attitudes of patients undergoing diagnostic imaging procedures that use ionizing radiation vary widely. Patient perception of radiation dose strongly influences their acceptance of diagnostic examinations or therapies involving radioactivity. Here, we review perceptions and concerns about radiation and radioactivity by laypersons and medical experts. Several studies show that physicians are frequently poorly informed about radiation levels associated with nuclear medicine and radiologic examinations. In addition, patients’ decisions against undergoing an imaging procedure are frequently based on partial and sometimes incorrect information. Thus, physicians must take the concerns of their patients seriously. From the literature and our own experience, we conclude that it is extremely important to thoroughly and carefully educate all involved in patient work-up about radiation exposure levels and perceived or actual health risks. Although the choice and timing of imaging examinations should always outweigh the risk that secondary illness will develop, the patients’ concerns still must be alleviated.