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.

     

Defining optimal tracer activities in pediatric oncologic whole-body <Superscript>18</Superscript>F-FDG-PET/MRI

Purpose

To explore the feasibility of reducing administered tracer activities and to assess optimal activities for combined ¹⁸F-FDG-PET/MRI in pediatric oncology.

Methods

30 ¹⁸F-FDG-PET/MRI examinations were performed on 24 patients with known or suspected solid tumors (10 girls, 14 boys, age 12?±?5.6 [1–18] years; PET scan duration: 4 min per bed position). Low-activity PET images were retrospectively simulated from the originally acquired data sets using randomized undersampling of list mode data. PET data of different simulated administered activities (0.25–2.5 MBq/kg body weight) were reconstructed with or without point spread function (PSF) modeling. Mean and maximum standardized uptake values (SUV_mean and SUV_max) as well as SUV variation (SUV_var) were measured in physiologic organs and focal FDG-avid lesions. Detectability of organ structures and of focal ¹⁸F-FDG-avid lesions as well as the occurrence of false-positive PET lesions were assessed at different simulated tracer activities.

Results

Subjective image quality steadily declined with decreasing tracer activities. Compared to the originally acquired data sets, mean relative deviations of SUV_mean and SUV_max were below 5 % at ¹⁸F-FDG activities of 1.5 MBq/kg or higher. Over 95 % of anatomic structures and all pathologic focal lesions were detectable at 1.5 MBq/kg ¹⁸F-FDG. Detectability of anatomic structures and focal lesions was significantly improved using PSF. No false-positive focal lesions were observed at tracer activities of 1 MBq/kg ¹⁸F-FDG or higher. Administration of ¹⁸F-FDG activities of 1.5 MBq/kg is, thus, feasible without obvious diagnostic shortcomings, which is equivalent to a dose reduction of more than 50 % compared to current recommendations.

Conclusion

Significant reduction in administered ¹⁸F-FDG tracer activities is feasible in pediatric oncologic PET/MRI. Appropriate activities of ¹⁸F-FDG or other tracers for specific clinical questions have to be further established in selected patient populations.

     

<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.

     

Incidental focal <Superscript>18</Superscript>F-FDG uptake in the frontal process of the maxilla on PET/CT: prevalence and clinical significance

Objective

We investigated the prevalence and clinical significance of incidental focal ¹⁸F-FDG uptake in the frontal process of the maxilla, mimicking malignancy on PET/CT.

Methods

From a total of 32,834 patients who underwent ¹⁸F-FDG PET/CT, patients with focal uptake in the frontal process of the maxilla were selected by a database search. For those patients, medical records including relevant imaging studies were reviewed.

Results

Thirty-nine patients (0.12 %) demonstrated focal uptake on PET/CT. On CT of PET/CT, all lesions showed ground-glass attenuation with or without bony expansion, consistent with fibrous dysplasia. When comparing previous PET/CT, follow-up PET/CT, and CT, a significant difference in degree of ¹⁸F-FDG uptake was noted, with no associated change in the size of maxillary lesions. There were no patients who had symptoms or signs related to maxillary lesions during follow-up.

Conclusion

Focal ¹⁸F-FDG uptake in the frontal process of the maxilla is a rare, incidental, and persistent finding with variable uptake and can represent a benign condition.

     

Quantitative assessment of atherosclerotic plaques on <Superscript>18</Superscript>F-FDG PET/MRI: comparison with a PET/CT hybrid system

Purpose

PET with ¹⁸F-FDG has the potential to assess vascular macrophage metabolism. ¹⁸F-FDG is most often used in combination with contrast-enhanced CT to localize increased metabolism to specific arterial lesions. Novel ¹⁸F-FDG PET/MRI hybrid imaging shows high potential for the combined evaluation of atherosclerotic plaques, due to the superior morphological conspicuity of plaque lesions. The purpose of this study was to evaluate the reliability and accuracy of ¹⁸F-FDG PET/MRI uptake quantification compared to PET/CT as a reference standard in patients with carotid atherosclerotic plaques.

Methods

The study group comprised 34 consecutive oncological patients with carotid plaques who underwent both PET/CT and PET/MRI with ¹⁸F-FDG on the same day. The presence of atherosclerotic plaques was confirmed by 3 T MRI scans. Maximum standardized uptake values (SUV_max) for carotid plaque lesions and the average SUV of the blood pool within the adjacent internal jugular vein were determined and target-to-blood ratios (TBRs, plaque to blood pool) were calculated.

Results

Atherosclerotic lesions with maximum colocalized focal FDG uptake were assessed in each patient. SUV_max values of carotid plaque lesions were significantly lower on PET/MRI than on PET/CT (2.3?±?0.6 vs. 3.1?±?0.6; P?<?0.01), but were significantly correlated between PET/CT and PET/MRI (Spearman’s r?=?0.67, P?<?0.01). In contrast, TBR_max values of plaque lesions were similar on PET/MRI and on PET/CT (2.2?±?0.3 vs. 2.2?±?0.3; P?=?0.4), and again were significantly correlated between PET/MRI and PET/CT (Spearman’s r?=?0.73, P?<?0.01). Considering the increasing trend in SUV_max and TBR_max values from early to delayed imaging time-points on PET/CT and PET/MRI, respectively, with continuous clearance of radioactivity from the blood, a slight underestimation of TBR_max values may also be expected with PET/MRI compared with PET/CT.

Conclusion

SUV_max and TBR_max values are widely accepted reference parameters for estimation of the radioactivity of atherosclerotic plaques on PET/CT. However, due to a systematic underestimation of SUV_max and TBR_max with PET/MRI, the optimal cut-off values indicating the presence of inflamed plaque tissue need to be newly defined for PET/MRI.

     

Clinical Significance of Incidental Focal <Superscript>18</Superscript>F-FDG Uptake in the Spinal Cord of Patients with Cancer

Purpose

We investigated the incidence, location, and clinical significance of focal ¹⁸F-FDG uptake of the spinal cord in patients with cancer.

Methods

We reviewed the medical records of 22,937 consecutive adult patients with known or suspicious malignancy who underwent ¹⁸F-FDG PET/CT. PET/CT scans with incidental focal spinal cord uptake were selected and retrospectively reviewed to determine the presence, location, number, and maximum standardized uptake value (SUV_max) of any focal hypermetabolic lesions of the spinal cord. In subjects with focal spinal uptake, clinical characteristics and clinical follow-up results, including follow-up PET/CT, were reviewed.

Results

Incidental focal spinal cord uptake was observed in 69 of 22,937 adult patients (incidence?=?0.3%; M:F?=?31:38; age, 55.8?±?14.7 years). Seventy-eight focal hypermetabolic lesions on spinal cord in the PET/CT scans of the 69 study subjects were analyzed. The most common sites of focal spinal cord uptake were the T12 vertebra (47/78; 60.3%) and L1 vertebra (20/78; 25.6%). Multifocal cord uptake was found in 8 of 69 patients (11.6%). The average SUV_max for cord uptake was 2.5?±?0.5 (range, 1.4～3.9). There was no clinical or imaging evidence of abnormalities in the spinal cord, both at the time of PET/CT and during clinical follow-up.

Conclusions

Although incidental focal ¹⁸F-FDG uptake of the spinal cord is rare in patients with cancer, it may be physiological or benign, but it should not be considered as malignant involvement. Common sites for the uptake were in the T12 and L1 spine levels.

     

Assessing the role of <Superscript>18</Superscript>F-FDG PET and <Superscript>18</Superscript>F-FDG PET/CT in the diagnosis of soft tissue musculoskeletal malignancies: a systematic review and meta-analysis

Purpose

Twelve years ago a meta-analysis evaluated the diagnostic performance of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in assessing musculoskeletal soft tissue lesions (MsSTL). Currently, PET/CT has substituted PET imaging; however, there has not been any published meta-analysis on the use of PET/CT or a comparison of PET/CT with PET in the diagnosis of MsSTL. Therefore, we conducted a meta-analysis to identify the current diagnostic performance of ¹⁸F-FDG PET/CT and determine if there is added value when compared to PET.

Methods

A systematic review of English articles was conducted, and MEDLINE PubMed, the Cochrane Library, and Embase were searched from 1996 to March 2015. Studies exploring the diagnostic accuracy of ¹⁸F-FDG PET/CT (or dedicated PET) compared to histopathology in patients with MsSTL undergoing investigation for malignancy were included.

Results

Our meta-analysis included 14 articles composed of 755 patients with 757 soft tissue lesions. There were 451 (60 %) malignant tumors and 306 benign lesions. The ¹⁸F-FDG PET/CT (and dedicated PET) mean sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for diagnosing MsSTL were 0.96 (0.90, 1.00), 0.77 (0.67, 0.86), 0.88 (0.85, 0.91), 0.86 (0.78, 0.94), and 0.91 (0.83, 0.99), respectively. The posterior mean (95 % highest posterior density interval) for the AUC was 0.92 (0.88, 0.96). PET/CT had higher specificity, accuracy, and positive predictive value when compared to a dedicated PET (0.85, 0.89, and 0.91 vs 0.71, 0.85, and 0.82, respectively).

Conclusion

¹⁸F-FDG PET/CT and dedicated PET are both highly accurate in the diagnosis of MsSTL. PET/CT is more accurate and specific and has a higher positive predictive value than PET.

     

Predictive value of <Superscript>18</Superscript>F-FDG PET/CT in restaging patients affected by ovarian carcinoma: a multicentre study

Purpose

Ovarian cancer is the eighth most common malignancy among women and has a high mortality rate. Prognostic factors able to drive an effective therapy are essential. ¹⁸F-Fluoro-2-deoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) has been investigated in patients with epithelial ovarian cancer and showed promise in diagnosing, staging, detecting recurrent lesions and monitoring treatment response. Conversely, its prognostic role remains unclear. We aimed at assessing the prognostic value of ¹⁸F-FDG PET/CT performed in the restaging process in a multicentre study.

Methods

We evaluated 168 patients affected by ovarian carcinoma, who underwent a restaging ¹⁸F-FDG PET/CT. The presence of local recurrences, lymph node involvement and distant metastasis was recorded as well as lesion dimensions, maximum and mean standardized uptake values (SUV_max and SUV_mean, respectively). Progression-free survival (PFS) and overall survival (OS) at 3 and 4 years were computed by using Kaplan-Meier curves. Increased odds ratio was assessed using Cox regression analysis testing all lesion parameters measured by PET/CT.

Results

PFS was significantly longer in patients with a negative than a positive restaging PET/CT study (3- and 4-year PFS 64 and 53 % vs 23 and 12 %, respectively; p?<?0.001). Similarly, a negative study was associated with a significantly higher OS rate after 4 years of follow-up (67 vs 25 % in negative and positive groups, respectively; p?<?0.001). Lymph node or distant involvement were also independently associated with an increased risk of disease progression [hazard ratio (HR) 1.6 and 2.2, respectively; p?=?0.003]. Moreover, PET/CT showed an incremental prognostic value compared to the International Federation of Gynecology and Obstetrics (FIGO) staging system. In the analysis of patient subsets, individuals with the same FIGO stage I–II but with negative PET had a significantly better 4-year OS than patients with low FIGO stage but positive PET. This implies that patients with the same FIGO stage can be further prognostically stratified using PET (p?=?0.01). At receiver-operating characteristic (ROC) analysis, no thresholds for semiquantitative parameters were predictive of a worse outcome.

Conclusion

¹⁸F-FDG PET/CT has an important prognostic value in assessing the risk of disease progression and mortality rate. An efficacious therapy planning might therefore effectively rely on ¹⁸F-FDG PET/CT findings. Semiquantitative data were not proven to be an effective tool to predict disease progression.

     

Treatment response evaluation with <Superscript>18</Superscript>F-FDG PET/CT and <Superscript>18</Superscript>F-NaF PET/CT in multiple myeloma patients undergoing high-dose chemotherapy and autologous stem cell transplantation

Aim

The aim of this study was to assess the combined use of the radiotracers ¹⁸F-FDG and ¹⁸F-NaF in treatment response evaluation of a group of multiple myeloma (MM) patients undergoing high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) by means of static (whole-body) and dynamic PET/CT (dPET/CT).

Patients and methods

Thirty-four patients with primary, previously untreated MM scheduled for treatment with HDT followed by ASCT were enrolled in the study. All patients underwent PET/CT scanning with ¹⁸F-FDG and ¹⁸F-NaF before and after therapy. Treatment response by means of PET/CT was assessed according to the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria. The evaluation of dPET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modelling and a non-compartmental approach leading to the extraction of fractal dimension (FD).

Results

An analysis was possible in 29 patients: three with clinical complete response (CR) and 26 with non-CR (13 patients near complete response-nCR, four patients very good partial response-VGPR, nine patients partial response-PR). After treatment, ¹⁸F-FDG PET/CT was negative in 14/29 patients and positive in 15/29 patients, showing a sensitivity of 57.5 % and a specificity of 100 %. According to the EORTC 1999 criteria, ¹⁸F-FDG PET/CT-based treatment response revealed CR in 14 patients (¹⁸F-FDG PET/CT CR), PR in 11 patients (¹⁸F-FDG PET/CT PR) and progressive disease in four patients (¹⁸F-FDG PET/CT PD). In terms of ¹⁸F-NaF PET/CT, 4/29 patients (13.8 %) had a negative baseline scan, thus failed to depict MM. Regarding the patients for which a direct lesion-to-lesion comparison was feasible, ¹⁸F-NaF PET/CT depicted 56 of the 129 ¹⁸F-FDG positive lesions (43 %). Follow-up ¹⁸F-NaF PET/CT showed persistence of 81.5 % of the baseline ¹⁸F-NaF positive MM lesions after treatment, despite the fact that 64.7 % of them had turned to ¹⁸F-FDG negative. Treatment response according to ¹⁸F-NaF PET/CT revealed CR in one patient (¹⁸F-NaF PET/CT CR), PR in five patients (¹⁸F-NaF PET/CT PR), SD in 12 patients (¹⁸F-NaF PET/CT SD), and PD in seven patients (¹⁸F-NaF PET/CT PD). Dynamic ¹⁸F-FDG and ¹⁸F-NaF PET/CT studies showed that SUV_average, SUV_max, as well as the kinetic parameters K₁, influx and FD from reference bone marrow and skeleton responded to therapy with a significant decrease (p?<?0.001).

Conclusion

F-FDG PET/CT demonstrated a sensitivity of 57.7 % and a specificity of 100 % in treatment response evaluation of MM. Despite its limited sensitivity, the performance of ¹⁸F-FDG PET/CT was satisfactory, given that 6/9 false negative patients in follow-up scans (66.7 %) were clinically characterized as nCR, a disease stage with very low tumor mass. On the other hand, ¹⁸F-NaF PET/CT does not seem to add significantly to ¹⁸F-FDG PET/CT in treatment response evaluation of MM patients undergoing HDT and ASCT, at least shortly after therapy.

     

Diagnostic value of combining <Superscript>11</Superscript>C-choline and <Superscript>18</Superscript>F-FDG PET/CT in hepatocellular carcinoma

Purpose

In this prospective study, our goal was to emphasize the diagnostic value of combining ¹¹C-choline and ¹⁸F-FDG PET/CT for hepatocellular carcinoma (HCC) in patients with chronic liver disease.

Methods

Thirty-three consecutive patients were enrolled. All patients were suspected to have HCC based on CT and/or MRI imaging. A final diagnosis was obtained by histopathological examination or by imaging alone according to American Association for the Study of Liver Disease criteria. All patients underwent PET/CT with both tracers within a median of 5 days. All lesions showing higher tracer uptake than normal liver were considered positive for HCC. We examined how tracer uptake was related to biological (serum α-fetoprotein levels) and pathological (differentiation status, peritumoral capsule and vascular invasion) prognostic markers of HCC, as well as clinical observations at 6 months (recurrence and death).

Results

Twenty-eight HCC, four cholangiocarcinomas and one adenoma were diagnosed. In the HCC patients, the sensitivity of ¹¹C-choline, ¹⁸F-FDG and combined ¹¹C-choline and ¹⁸F-FDG PET/CT for the detection of HCC was 75 %, 36 % and 93 %, respectively. Serum α-fetoprotein levels >200 ng/ml were more frequent among patients with ¹⁸F-FDG-positive lesions than those with ¹⁸F-FDG-negative lesions (p?<?0.05). Early recurrence (n=2) or early death (n=5) occurred more frequently in patients with ¹⁸F-FDG-positive lesions than in those with ¹⁸F-FDG-negative lesions (p?<?0.05).

Conclusion

The combined use of ¹¹C-choline and ¹⁸F-FDG PET/CT detected HCC with high sensitivity. This approach appears to be of potential prognostic value and may facilitate the selection of patients for surgical resection or liver transplantation.

     

Influence of <Superscript>18</Superscript>F-FDG PET/CT on therapy management in patients with stage III/IV malignant melanoma

Purpose

To evaluate the influence of ¹⁸F-FDG PET/CT in comparison to CT alone on treatment decisions in patients with advanced melanoma and to analyse the 5-year survival data in comparison to literature data.

Methods

Therapy management in 64 consecutive patients (primary staging n?=?52; surveillance n?=?12) with stage III/IV melanoma who underwent ¹⁸F-FDG PET/CT between 2004 and 2005 in our department was retrospectively analysed. Treatment decisions were made by two dermatooncologists for each patient twice, first based on the CT results and then based on the PET/CT results. Therapy changes based on the PET/CT results were classified as “major” (e.g. change from metastasectomy to systemic therapy) or “minor” (e.g. change from first to second line chemotherapy). The 5-year survival data of different patient cohorts were calculated.

Results

In the 52 patients in the primary staging group, the results of ¹⁸F-FDG PET/CT led to therapy change in 59 % and a major therapy change in 52 %. ¹⁸F-FDG PET/CT led to the avoidance of futile operations in 13 patients with suspicious lesions on CT that were deemed nontumorous on PET/CT. In the 12 patients in the surveillance group, the results of ¹⁸F-FDG PET/CT led to therapy change in 33 % and a major change in 17 %. The 5-year survival rates were 30 % in the entire cohort, 34 % in the primary staging group, and 17 % in the surveillance group. A significant overall survival benefit was observed in patients in whom ¹⁸F-FDG PET/CT excluded metastases or in whom metastases could be completely removed compared with patients who were not eligible for surgery (41 % vs. 10 %).

Conclusion

Primary staging of patients with stage III/IV melanoma should be performed with ¹⁸F-FDG PET/CT, leading to higher diagnostic accuracy and enabling individualized therapeutic management, especially optimal patient selection for metastasectomy. This strategy may extend long-term survival even in patients with advanced disease.

     

<Superscript>18</Superscript>F-fluorodeoxyglucose positron emission tomography-computed tomography in the management of adult multisystem Langerhans cell histiocytosis

Purpose

The standard evaluation of multisystem Langerhans cell histiocytosis (LCH) includes a clinical evaluation, laboratory tests and a skeleton/skull X-ray survey, with chest high-resolution computed tomography (HRCT) in the case of pulmonary involvement. Preliminary reports suggest that ¹⁸F-fluorodeoxyglucose positron emission tomography-computed tomography (¹⁸F-FDG PET-CT) may be useful for evaluating patients with LCH.

Methods

Fourteen consecutive adult patients with multisystem LCH were included in this retrospective study, and were evaluated using standard procedures and ¹⁸F-FDG PET-CT. The two sets of findings were compared both at baseline and during follow-up. Serial HRCT and pulmonary function tests were used to evaluate outcome in patients with lung involvement.

Results

At the baseline evaluation, PET-CT identified every LCH localization found with the standard evaluation (except a mild cecum infiltration). PET-CT showed additional lesions in seven patients, mostly involving bones, and differentiated inactive from active lesions. Thyroid ¹⁸F-FDG uptake was identified in three cases. No pituitary stalk ¹⁸F-FDG uptake was observed in patients with pituitary LCH. Only 3/12 (25 %) patients with pulmonary LCH displayed moderate pulmonary ¹⁸F-FDG uptake. During follow-up, variations (≥50 % of maximum standardized uptake) in bone ¹⁸F-FDG uptake intensity were correlated with disease state and response to treatment. The absence of lung ¹⁸F-FDG uptake did not preclude lung function improvement after treatment.

Conclusions

Except for cases with pulmonary and pituitary involvement, ¹⁸F-FDG PET-CT could replace the standard evaluation for staging of adult patients with multisystem LCH. Serial PET-CT scans are useful for evaluating treatment responses, particularly in cases with bone LCH involvement.

     

Different predictive values of interim <Superscript>18</Superscript>F-FDG PET/CT in germinal center like and non-germinal center like diffuse large B-cell lymphoma

Purpose

Diffuse large B-cell lymphoma (DLBCL) is a pathologically heterogeneous disease with different prognoses according to its molecular profiles. Despite the broad usage of ¹⁸F-fluoro-2-dexoxy-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT), previous studies that have investigated the value of interim ¹⁸F-FDG PET/CT in DLBCL have given the controversial results. The purpose of this study was to evaluate the prognostic value of interim ¹⁸F-FDG PET/CT in DLBCL according to germinal center B cell-like (GCB) and non-GCB molecular profiling.

Methods

We enrolled 118 newly diagnosed DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). Interim ¹⁸F-FDG PET/CT scans performed after 2 or 3 cycles of R-CHOP treatment were evaluated based on the Lugano response criteria. Patients were grouped as GCB or non-GCB molecular subtypes according to immunohistochemistry results of CD10, BCL6, and MUM1, based on Hans’ algorithm.

Results

In total 118 DLBCL patients, 35 % were classified as GCB, and 65 % were classified as non-GCB. Interim PET/CT was negative in 70 %, and positive in 30 %. During the median follow-up period of 23 months, the positive interim ¹⁸F-FDG PET/CT group showed significantly inferior progression free survival (PFS) compared to the negative interim ¹⁸F-FDG PET/CT group (P = 0.0004) in entire patients. A subgroup analysis according to molecular profiling demonstrated significant difference of PFS between the positive and negative interim ¹⁸F-FDG PET groups in GCB subtype of DLBCL (P = 0.0001), but there was no significant difference of PFS between the positive and negative interim ¹⁸F-FDG PET groups in non-GCB subtype of DLBCL.

Conclusions

Interim ¹⁸F-FDG PET/CT scanning had a significant predictive value for disease progression in patients with the GCB subtype of DLBCL treated with R-CHOP, but not in those with the non-GCB subtype. Therefore, molecular profiles of DLBCL should be considered for interim ¹⁸F-FDG PET/CT practice.

     

Inverse Prognostic Relationships of <Superscript>18</Superscript>F-FDG PET/CT Metabolic Parameters in Patients with Distal Bile Duct Cancer Undergoing Curative Surgery

Purpose

As there were few previous studies with a small number of subjects, the purpose of this was to evaluate the prognostic significance of ¹⁸F-FDG PET/CT in patients with distal bile duct cancer undergoing curative surgery.

Methods

The study included 40 patients (M/F?=?24:16; age 68.0?±?8.0 years) who underwent preoperative ¹⁸F-FDG PET/CT followed by curative surgical resection. The participant’s age, sex, Eastern Cooperative Oncology Group performance-status score, baseline serum CA 19-9 level, stage, pathologic T and N stages, tumor size, tumor grade, tumor growth pattern, R0 resection, and adjuvant therapy were included as clinicopathological variables for predicting overall survival. The PET variables were maximum standardized uptake value (SUV_max), average SUV (SUV_avg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the tumor. The Kaplan-Meyer method and Cox proportional hazards model were used for the survival analysis.

Results

A total of 15 of 40 patients (37.5%) died during the follow-up period. In univariate analysis, low SUV_max (≤?2.7, p?=?0.0005) and low SUV_avg (≤?2.6, p?=?0.0034) were significant predictors of poor overall survival. In multivariate analyses, only low SUV_max (HR?=?6.7016, 95% CI 1.9961–22.4993, p?=?0.0047) was an independent prognostic factor associated with poor overall survival.

Conclusion

The SUV_max of the primary tumor measured by ¹⁸F-FDG PET/CT was an independent significant prognostic factor for overall survival in patients with distal bile duct cancer. However, different results from a previous study warrant further large sample-sized study.

     

Multimodal imaging with <Superscript>18</Superscript>F-FDG-PET/CT and <Superscript>111</Superscript>In-Octreotide SPECT in patients with metastatic medullary thyroid carcinoma

Objective

The aim of our study was to determine the role of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) and indium-111 Octreotide single photon emission tomography (¹¹¹In-Octreotide SPECT) in the evaluation of metastatic medullary thyroid carcinoma (MMTC).

Methods

Twenty-five MMTC patients were retrospectively evaluated. All patients had undergone whole-body ¹⁸F-FDG-PET/CT including 20 who had also undergone ¹¹¹In-Octreotide SPECT within a maximum interval of 6 weeks. Diagnostic contrast-enhanced computed tomography (CT) alone or as part of ¹⁸F-FDG-PET/CT examination was performed in all patients.

Results

Contrast-enhanced CT detected a total of 131 lesions including 79 enlarged lymph nodes and 14 bone lesions. ¹⁸F-FDG-PET/CT visualized a total of 92 true positive lesions (SUV_max range 1.1–10.0, mean 4.0 ± 1.7) including 66 lymph nodes, 7 of which were not enlarged on CT, and 8 bone metastases. In the 20 patients studied with both techniques, a total of 64 and 46 true positive lesions were detected by ¹⁸F-FDG-PET/CT and ¹¹¹In-Octreotide SPECT, respectively. In particular, ¹⁸F-FDG uptake was found in 43 lymph nodes and in 7 bone metastases whereas ¹¹¹In-Octreotide uptake was detected in 27 lymph nodes and in 10 bone metastases.

Conclusions

In MMTC patients, ¹⁸F-FDG-PET/CT provides a useful contribution mainly in evaluating lymph node involvement whereas ¹¹¹In-Octreotide SPECT can contribute to the detection and somatostatin receptor characterization especially of bone lesions.

     

<Superscript>18</Superscript>F-FDG uptake by rectal cancer is similar in mucinous and nonmucinous histological subtypes

Purpose

PET/CT has been considered limited for the evaluation of mucinous colorectal tumors due to low ¹⁸F-FDG uptake. The aim of our study was to compare PET/CT variables in mucinous (MC) and nonmucinous (NMC) rectal adenocarcinomas.

Methods

Consecutive patients with cT2-4N0-2M0 rectal cancer included in a prospective clinical trial were reviewed. PET/CT was performed for primary baseline staging. Visual and quantitative analysis included SUVmax and SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG). PET/CT parameters were compared according to histological subtypes.

Results

Overall, 73 patients were included (18 mucinous and 55 nonmucinous). SUVmax values were similar between MC and NMC (19.7 vs. 16.6; p = 0.5). MTV and TLG values were greater in the MC group (103.9 vs. 54.1; p = 0.007 and 892.5 vs. 358.8; p = 0.020) due to larger tumor volumes of MC.

Conclusions

Metabolic parameters at baseline PET/CT for patients with rectal cancer are similar in mucinous and nonmucinous histological subtypes.

     

Current generation time-of-flight <Superscript>18</Superscript>F-FDG PET/CT provides higher SUVs for normal adrenal glands,while maintaining an accurate characterization of benign and malignant glands

Objective

Modern PET/CT scanners have significantly improved detectors and fast time-of-flight (TOF) performance and this may improve clinical performance. The aim of this study was to analyze the impact of a current generation TOF PET/CT scanner on standardized uptake values (SUV), lesion-background contrast and characterization of the adrenal glands in patients with suspected lung cancer, in comparison with literature data and commonly used SUV cut-off levels.

Methods

We included 149 adrenal glands from 88 patients with suspected lung cancer, who underwent ¹⁸F-FDG PET/CT. We measured the SUV_max in the adrenal gland and compared this with liver SUV_mean to calculate the adrenal-to-liver ratio (AL ratio). Results were compared with literature derived with older scanners, with SUV_max values of 1.0 and 1.8 for normal glands [1, 2]. Final diagnosis was based on histological proof or follow-up imaging. We proposed cut-off values for optimal separation of benign from malignant glands.

Results

In 127 benign and 22 malignant adrenal glands, SUV_max values were 2.3 ± 0.7 (mean ± SD) and 7.8 ± 3.2 respectively (p < 0.01). Corresponding AL ratios were 1.0 ± 0.3 and 3.5 ± 1.4 respectively (p < 0.01). With a SUV_max cut-off value of 3.7, 96 % sensitivity and 96 % specificity was reached. An AL ratio cut-off value of 1.8 resulted in 91 % sensitivity and 97 % specificity. The ability of both SUV_max and AL ratio to separate benign from malignant glands was similar (AUC 0.989 vs. 0.993, p = 0.22).

Conclusions

Compared with literature based on the previous generation of PET scanners, current generation TOF ¹⁸F-FDG PET/CT imaging provides higher SUVs for benign adrenal glands, while it maintains a highly accurate distinction between benign and malignant glands. Clinical implementation of current generation TOF PET/CT requires not only the use of higher cut-off levels but also visual adaptation by PET readers.

     

Diagnostic utility of PET/CT with <Superscript>18</Superscript>F-DOPA and <Superscript>18</Superscript>F-FDG in persistent or recurrent medullary thyroid carcinoma: the importance of calcitonin and carcinoembryonic antigen cutoff

Purpose

This study sought to evaluate and compare the utility of 18-F-fluorodihydroxyphenylalanine (¹⁸F-DOPA) and 18-F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) for identification of lesions in patients with recurrent medullary thyroid carcinoma (MTC). In addition, we analyzed the correlation between the calcitonin (Ct), carcinoembryonic antigen (CEA) levels, each doubling time (DT), and PET positivity. We evaluated the reliability of the 150 pg/mL Ct cutoff set by the American Thyroid Association guidelines for further imaging (including ¹⁸F-DOPA PET/CT).

Methods

We prospectively recruited 18 patients with recurrent MTC, identified by elevation of Ct or CEA. Each patient underwent a ¹⁸F-FDG PET/CT and a ¹⁸F-DOPA PET/CT.

Results

Abnormal uptakes were detected with ¹⁸F-DOPA (n=12) and ¹⁸F-FDG (n=9), (sensitivity of 66.7% vs. 50%; p<0.01). Twenty-eight lesions were detected with ¹⁸F-DOPA vs. 16 lesions with ¹⁸F-FDG (1.56±1.5 vs. 0.89±1.18 lesions per patient; p=0.01). None of our patients showed additional lesions with ¹⁸F-FDG in comparison to ¹⁸F-DOPA. Patient-based detection rate increased significantly with Ct levels ≥150 pg/mL vs. Ct<150 pg/mL for both ¹⁸F-DOPA (sensitivity 90.9% vs. 28.6%; p=0.013) and ¹⁸F-FDG PET/CT (sensitivity 72.7% vs. 14.3%; p=0.025). Using a CEA cutoff of ≥5 ng/mL, detection rates of ¹⁸F-DOPA and ¹⁸F-FDG PET/CT were 81.1% and 72.7%, respectively. No correlation between Ct-DT or CEA-DT and PET positivity was found. Histological confirmation was obtained in eight patients.

Conclusions

¹⁸F-DOPA PET/CT appears to be superior to ¹⁸F-FDG PET/CT in detecting and locating lesions in patients with recurrent MTC. This technique tends to be especially useful in patients with negative results in other imaging modalities and Ct≥150 pg/mL or CEA≥5 ng/mL.

     

Absolute number of new lesions on <Superscript>18</Superscript>F-FDG PET/CT is more predictive of clinical response than SUV changes in metastatic melanoma patients receiving ipilimumab

Purpose

Evaluation of response to immunotherapy is a matter of debate. The aim of the present study was to evaluate the response of metastatic melanoma to treatment with ipilimumab by means of ¹⁸F-FDG PET/CT, using the patients’ clinical response as reference.

Methods

The final cohort included in the analyses consisted of 41 patients with metastatic melanoma who underwent ¹⁸F-FDG PET/CT before and after administration of ipilimumab. After determination of the best clinical response, the PET/CT scans were reviewed and a separate independent analysis was performed, based on the number and functional size of newly emerged ¹⁸F-FDG-avid lesions, as well as on the SUV changes after therapy.

Results

The median observation time of the patients after therapy was 21.4 months (range 6.3–41.9 months). Based on their clinical response, patients were dichotomized into those with clinical benefit (CB) and those without CB (No-CB). The CB group (31 patients) included those with stable disease, partial remission and complete remission, and the No-CB group (10 patients) included those with progressive disease. The application of a threshold of four newly emerged ¹⁸F-FDG-avid lesions on the posttherapy PET/CT scan led to a sensitivity (correctly predicting CB) of 84% and a specificity (correctly predicting No-CB) of 100%. This cut-off was lower for lesions with larger functional diameters (three new lesions larger than 1.0 cm and two new lesions larger than 1.5 cm). SUV changes after therapy did not correlate with clinical response. Based on these findings, we developed criteria for predicting clinical response to immunotherapy by means of ¹⁸F-FDG PET/CT (PET Response Evaluation Criteria for Immunotherapy, PERCIMT).

Conclusion

Our results show that a cut-off of four newly emerged ¹⁸F-FDG-avid lesions on posttherapy PET/CT gives a reliable indication of treatment failure in patients under ipilimumab treatment. Moreover, the functional size of the new lesions plays an important role in predicting the clinical response. Validation of these results in larger cohorts of patients is warranted.

     

Prognostic value of <Superscript>18</Superscript>F-fluorodeoxyglucose positron emission tomography in patients with gastric neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma

Objective

Gastric neuroendocrine carcinomas (NEC) and mixed adenoneuroendocrine carcinoma (MANEC) are very rare, aggressive tumors of the stomach. We aimed to examine predictive role of pretreatment ¹⁸F-FDG PET/CT-assessed metabolic parameter of primary tumors and metastases in patients with gastric NEC and MANEC.

Methods

We conducted a review of the 27 patients with histopathologically confirmed NECs (n = 10) and MANEC (n = 17) of the stomach at our institution between January 2005 and December 2012. All patients underwent ¹⁸F-FDG-PET examination at diagnosis. Metabolic parameters [SUV_max, SUV_mean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG)] of the primary tumor and metastases on baseline PET/CT were analyzed.

Results

The median follow-up duration was 39.4 months (95 % CI 20.0–58.1 months) and the median overall survival (OS) was 25.7 months (95 % CI 14.1–37.2 months). All gastric lesions were well visualized (average SUV_max = 12.0, range 3.0–41.8). When subjects were divided into two groups by ROC cut-off value of 210.9 and 612, patients with high TLG in primary lesion and metastases showed poorer prognosis compared to low TLG patients (P = 0.09, P = 0.002, respectively). In the sub-analysis of patients with metastasis (n = 12), patients with high TLG in whole body tumor showed significantly shorter OS compared to those with low TLG (31.7 ± 11.4 vs. 7.2 ± 2.1 months, P = 0.006).

Conclusion

¹⁸F-FDG PET/CT is useful in evaluating prognosis of advanced gastric cancer with neuroendocrine carcinoma components. Baseline MTV of primary gastric cancer with metastatic disease, and MTV, TLG of metastases may be prognostic markers in patients with gastric NEC and MANEC.