<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.

     

Correlation of <Superscript>18</Superscript>F-FDG and <Superscript>11</Superscript>C-methionine uptake on PET/CT with Ki-67 immunohistochemistry in newly diagnosed intracranial meningiomas

Objective

We evaluated the uptake of 2-deoxy-2-¹⁸F-fluoro-d-glucose (FDG) and l-[methyl-¹¹C]-methionine (MET) in patients with newly diagnosed intracranial meningiomas and correlated the results with tumor proliferation.

Methods

Data from 22 patients with newly diagnosed intracranial meningioma (12 grade I and 10 grade II) who underwent both FDG and MET brain PET/CT studies were retrospectively analyzed. The PET images were evaluated by a qualitative method and semiquantitative analysis using standardized uptake value (SUV) (SUV_max and SUV_peak) and tumor-to-reference tissue ratio (T_max/N ratio and T_peak/N ratio). Proliferative activity as indicated by the Ki-67 index was estimated in tissue specimens.

Results

MET PET/CT showed a higher detection rate of meningioma than did FDG PET/CT (100 vs. 46%, respectively). The T_max/N ratio and T_peak/N ratio on MET PET/CT were significantly higher than those on FDG PET/CT (p?<?0.001 and p?<?0.001, respectively). There was a significant difference between grades I and II with respect to FDG SUVmax (p?=?0.003), FDG SUV_peak (p?=?0.003), FDG T_max/N ratio (p?=?0.02), FDG T_peak/N ratio (p?=?0.006), MET SUV_max (p?=?0.002), MET SUV_peak (p?=?0.002), MET T_max/N ratio (p?=?0.002), and MET T_peak/N ratio (p?=?0.002). There was a significant correlation between Ki-67 index and FDG PET/CT for SUV_max (p?=?0.02), SUV_peak (p?=?0.005), and T_peak/N ratio (p?=?0.05) and between Ki-67 index and MET PET/CT for SUV_max (p?=?0.004), SUV_peak (p?=?0.007), T_max/N ratio (p?=?0.002), and T_peak/N ratio (p?=?0.004).

Conclusion

MET PET/CT showed a high sensitivity compared with FDG PET/CT for detection of newly diagnosed WHO grades I and II intracranial meningiomas. Both FDG and MET uptake were found to be useful for evaluating tumor proliferation in meningiomas.

     

Repeatability of hypoxia PET imaging using [<Superscript>18</Superscript>F]HX4 in lung and head and neck cancer patients: a prospective multicenter trial

Purpose

Hypoxia is an important factor influencing tumor progression and treatment efficacy. The aim of this study was to investigate the repeatability of hypoxia PET imaging with [¹⁸F]HX4 in patients with head and neck and lung cancer.

Methods

Nine patients with lung cancer and ten with head and neck cancer were included in the analysis (NCT01075399). Two sequential pretreatment [¹⁸F]HX4 PET/CT scans were acquired within 1 week. The maximal and mean standardized uptake values (SUV_max and SUV_mean) were defined and the tumor-to-background ratios (TBR) were calculated. In addition, hypoxic volumes were determined as the volume of the tumor with a TBR >1.2 (HV_1.2). Bland Altman analysis of the uptake parameters was performed and coefficients of repeatability were calculated. To evaluate the spatial repeatability of the uptake, the PET/CT images were registered and a voxel-wise comparison of the uptake was performed, providing a correlation coefficient.

Results

All parameters of [¹⁸F]HX4 uptake were significantly correlated between scans: SUV_max (r?=?0.958, p?<?0.001), SUV_mean (r?=?0.946, p?<?0.001), TBR_max (r?=?0.962, p?<?0.001) and HV_1.2 (r?=?0.995, p?<?0.001). The relative coefficients of repeatability were 15 % (SUV_mean), 17 % (SUV_max) and 17 % (TBR_max). Voxel-wise analysis of the spatial uptake pattern within the tumors provided an average correlation of 0.65?±?0.14.

Conclusion

Repeated hypoxia PET scans with [¹⁸F]HX4 provide reproducible and spatially stable results in patients with head and neck cancer and patients with lung cancer. [¹⁸F]HX4 PET imaging can be used to assess the hypoxic status of tumors and has the potential to aid hypoxia-targeted treatments.

     

Comparison of [<Superscript>68</Superscript>Ga]Ga-PSMA-11 PET/CT with [<Superscript>18</Superscript>F]NaF PET/CT in the evaluation of bone metastases in metastatic prostate cancer patients prior to radionuclide therapy

Aim

The purpose of this study was to investigate the diagnostic performance of ⁶⁸Ga-PSMA-11 PET/CT in the evaluation of bone metastases in metastatic prostate cancer (PC) patients scheduled for radionuclide therapy in comparison to [¹⁸F]sodium fluoride (¹⁸F-NaF) PET/CT.

Methods

Sixteen metastatic PC patients with known skeletal metastases, who underwent both ⁶⁸Ga-PSMA-11 PET/CT and ¹⁸F-NaF PET/CT for assessment of metastatic burden prior to radionuclide therapy, were analysed retrospectively. The performance of both tracers was calculated on a lesion-based comparison. Intensity of tracer accumulation of pathologic bone lesions on ¹⁸F-NaF PET and ⁶⁸Ga-PSMA-11 PET was measured with maximum standardized uptake values (SUV_max) and compared to background activity of normal bone. In addition, SUV_max values of PET-positive bone lesions were analysed with respect to morphologic characteristics on CT. Bone metastases were either confirmed by CT or follow-up PET scan.

Results

In contrast to 468 PET-positive lesions suggestive of bone metastases on ¹⁸F-NaF PET, only 351 of the lesions were also judged positive on ⁶⁸Ga-PSMA-11 PET (75.0%). Intensity of tracer accumulation of pathologic skeletal lesions was significantly higher on ¹⁸F-NaF PET compared to ⁶⁸Ga-PSMA-11 PET, showing a median SUV_max of 27.0 and 6.0, respectively (p?<?0.001). Background activity of normal bone was lower on ⁶⁸Ga-PSMA-11 PET, with a median SUV_max of 1.0 in comparison to 2.7 on ¹⁸F-NaF PET; however, tumour to background ratio was significantly higher on ¹⁸F-NaF PET (9.8 versus 5.9 on ⁶⁸Ga-PSMA-11 PET; p?=?0.042). Based on morphologic lesion characterisation on CT, ¹⁸F-NaF PET revealed median SUV_max values of 23.6 for osteosclerotic, 35.0 for osteolytic, and 19.0 for lesions not visible on CT, whereas on ⁶⁸Ga-PSMA-11 PET median SUV_max values of 5.0 in osteosclerotic, 29.5 in osteolytic, and 7.5 in lesions not seen on CT were measured. Intensity of tracer accumulation between¹⁸F-NaF PET and ⁶⁸Ga-PSMA-11 PET was significantly higher in osteosclerotic (p?<?0.001) and lesions not visible on CT (p?=?0.012).

Conclusion

In comparison to ⁶⁸Ga-PSMA-11 PET/CT, ¹⁸F-NaF PET/CT detects a higher number of pathologic bone lesions in advanced stage PC patients scheduled for radionuclide therapy. Our data suggest that ⁶⁸Ga-PSMA-11 PET should be combined with ¹⁸F-NaF PET in PC patients with skeletal metastases for restaging prior to initiation or modification of therapy.

     

Usefulness of MRI-assisted metabolic volumetric parameters provided by simultaneous <Superscript>18</Superscript>F-fluorocholine PET/MRI for primary prostate cancer characterization

Purpose

The aim of this study was to determine the usefulness of MRI-assisted positron emission tomography (PET) parameters provided by simultaneous ¹⁸F-fluorocholine (FCH) PET/MRI for characterization of primary prostate cancer.

Methods

Thirty patients with localized prostate cancer (mean age 69.4?±?6.7 years) confirmed by biopsy were prospectively enrolled for simultaneous PET/MRI imaging. The patients underwent ¹⁸F-FCH PET/MRI 1 week before undergoing total prostatectomy. Multiple parameters of diffusion-weighted MRI [minimum and mean apparent diffusion coefficient (ADC_min and ADC_mean)], metabolic PET [maximum and mean standardized uptake value (SUV_max and SUV_mean)], and metabolic volumetric PET [metabolic tumor volume (MTV) and uptake volume product (UVP)] were compared with laboratory, pathologic, and immunohistochemical (IHC) features of the prostate cancer specimen. PET parameters were divided into two categories as follows: volume of interest (VOI) of prostate by SUV cutoff 2.5 (SUV_max, SUV_mean, MTV_SUV, and UVP_SUV) and MRI-assisted VOI of prostate cancer (SUV_maxMRI, SUV_meanMRI, MTV_MRI, and UVP_MRI).

Results

The rates of prostate cancer-positive cases identified by MRI alone, ¹⁸F-FCH PET alone, and ¹⁸F-FCH PET/MRI were 83.3, 80.0, and 93.3 %, respectively. Among the multiple PET/MRI parameters, MTV_MRI showed fair correlation with serum prostate-specific antigen (PSA; r?=?0.442, p?=?0.014) and highest correlation with tumor volume (r?=?0.953, p?<?0.001). UVP_MRI showed highest correlation with serum PSA (r?=?0.531, p?=?0.003), good correlation with tumor volume (r?=?0.908, p?<?0.001), and it was significantly associated with Gleason score (p?=?0.041). High MTV_MRI and UVP_MRI values were significant for perineural invasion, lymphatic invasion, extracapsular extension, seminal vesicle invasion, and positive B-cell lymphoma 2 (Bcl-2) expression (all p?<?0.05).

Conclusion

Simultaneous ¹⁸F-FCH PET/MRI demonstrated a better diagnostic value for localized prostate cancer detection than each individual modality. MRI-assisted metabolic volumetric PET parameters (MTV_MRI and UVP_MRI) provided more accurate characterization of prostate cancer than conventional PET and MRI parameters.

     

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.

     

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

Objectives

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

Methods

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

Results

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

Conclusions

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

     

Measurement of <Superscript>68</Superscript>Ga-DOTATOC Uptake in the Thoracic Aorta and Its Correlation with Cardiovascular Risk

Purpose

⁶⁸Ga-labeled 1,4,7,10-tetraazacyclododecane-N,N′,N″,N?-tetraacetic acid-d-Phe¹-Tyr³-octreotide (⁶⁸Ga-DOTATOC) is taken up by activated macrophages, which accumulate in active inflammatory lesions. The purpose of this study was to investigate the feasibility of ⁶⁸Ga-DOTATOC PET/CT for assessment of vulnerable plaque, by evaluating correlation between aortic uptake of ⁶⁸Ga-DOTATOC and cardiovascular risk factors.

Methods

Fifty patients with neuroendocrine tumors who underwent ⁶⁸Ga-DOTATOC PET/CT were retrospectively enrolled. The uptakes in the thoracic aorta were measured by two methods: multi-sample region-of-interest (ROI) method and single volume-of-interest (VOI) method. TBR_max-avg, TBR_mean-avg, TBR_max-VOI, and TBR_mean-VOI were defined by maximum and mean target-to-background ratio (TBR) from the multi-sample ROI method and the single VOI method, respectively.

Results

Framingham risk score (FRS) exhibited significant correlations with TBR_max-avg and TBR_mean-avg, as well as TBR_max-VOI (r?=?0.3389–0.4593, P?<?0.05 for all). TBR_max-avg and TBR_max-VOI were significantly higher in high FRS group than in low FRS group (1.48?±?0.21 vs. 1.70?±?0.17, P?<?0.001 for TBR_max-avg and 1.90?±?0.33 vs. 2.25?±?0.36, P?=?0.002 for TBR_max-VOI). TBR exhibited high correlations between the two measuring methods (r?=?0.9684, P?<?0.001 for TBR_mean-avg and TBR_mean-VOI and r?=?0.8681, P?<?0.001 for TBR_max-avg and TBR_max-VOI).

Conclusions

⁶⁸Ga-DOTATOC uptake in the thoracic aorta exhibited a significant correlation with cardiovascular risk factors, which suggests the feasibility of ⁶⁸Ga-DOTATOC PET for vulnerable plaque imaging, with a simple measurement of the single VOI method that is comparable to the multi-sample ROI-based approach.

     

Role of <Superscript>18</Superscript>F-FDG PET/CT in patients affected by Langerhans cell histiocytosis

Purpose

Langerhans cell histiocytosis (LCH) is a rare hematological disorder for which the utility of¹⁸F-FDG PET/CT is unclear. Our aim was to explore the metabolic features of LCH and the possible role of¹⁸F-FDG PET/CT in LCH evaluation.

Materials and methods

We found 17 patients with histologically proven LCH who underwent 17¹⁸F-FDG PET/CT scans for staging and 42 scans for restaging/follow-up purposes. PET/CT results were compared with those obtained from other conventional imaging modalities (bone scintigraphy, plain radiogram, computed tomography, magnetic resonance).

Results

¹⁸F-FDG PET/CT was positive in 15/17 patients, and it detected 36/37 lesions; all bone and extraskeletal lesions, except for a cecal lesion, were¹⁸F-FDG-avid. Only 1/4 of the patients with lung LCH had hypermetabolic lesions. The average SUV_max of the FDG-avid lesions was 7.3 ± 6.7, the average lesion-to-liver SUV_max ratio was 3.4 ± 2.5, and the average lesion-to-blood pool SUV_max ratio was 4 ± 3.2. In comparison to other imaging methods,¹⁸F-FDG PET/CT detected additional lesions or was able to evaluate treatment response earlier in 33/74 cases; it was confirmatory in 38/74 and detected fewer lesions in 3/74 (all three with lung LCH).

Conclusions

¹⁸F-FDG PET/CT seems to be useful for evaluating LCH when compared to conventional imaging, except in pulmonary cases. It can be used both for staging and restaging purposes.

     

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.

     

Evaluation of <Superscript>68</Superscript>Ga-DOTATOC PET/MRI for whole-body staging of neuroendocrine tumours in comparison with <Superscript>68</Superscript>Ga-DOTATOC PET/CT

Objectives

To compare the diagnostic performance of ⁶⁸Ga-DOTATOC PET/MRI and ⁶⁸Ga-DOTATOC PET/CT in the whole-body staging of patients with neuroendocrine tumours (NET).

Methods

Thirty patients with histopathologically confirmed NET underwent PET/CT and PET/MRI in a single-injection protocol. PET/CT and PET/MRI scans were prospectively evaluated with regard to lesion count, localization, nature (NET/non-NET), and conspicuity (four-point scale). Histopathology and follow-up imaging served as the reference standards. The proportions of NET and non-NET lesions rated correctly were compared using McNemar’s chi-squared test. The Wilcoxon test was used to assess differences in SUVmax and lesion conspicuity. The correlation between the SUVmax for the same lesions from each modality was analysed using Pearson’s correlation coefficient (r).

Results

According to the reference standard, there were 197 lesions (142 NET, 55 non-NET). Lesion-based analysis showed a higher proportion of correctly rated NET lesions on PET/MRI than on PET/CT (90.8% vs. 86.7%, p?=?0.031), whereas on PET/CT there was a higher proportion of correctly rated non-NET lesions (94.5% vs. 83.6%, p?=?0.031). SUVmax was strongly correlated (r?=?0.86; p?<?0.001) and did not differ significantly (p?=?0.35) between the modalities. Overall conspicuity and NET lesion conspicuity were higher on PET/MRI (both p?<?0.01).

Conclusions

Ga-DOTATOC PET/MRI yielded a higher proportion of correctly rated NET lesions and should be regarded as a valuable alternative to ⁶⁸Ga-DOTATOC PET/CT in whole-body staging of NET patients.

Key Points

? ⁶⁸ Ga-DOTATOC PET/MRI correctly identified more NET lesions than ⁶⁸ Ga-DOTATOC PET/CT. ? ⁶⁸ Ga-DOTATOC PET/MRI provides better NET lesion conspicuity than ⁶⁸ Ga-DOTATOC PET/CT. ? SUVmax values from the two modalities are strongly correlated and do not differ significantly.

     

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.

     

<Superscript>18</Superscript>F-alfatide PET/CT may predict short-term outcome of concurrent chemoradiotherapy in patients with advanced non-small cell lung cancer

Purpose

The study aims to investigate the role of ¹⁸F-alfatide positron emission tomography/computed tomography (PET/CT) in predicting the short-term outcome of concurrent chemoradiotherapy (CCRT) in patients with advanced non-small cell lung cancer (NSCLC).

Methods

Eighteen patients with advanced NSCLC had undergone ¹⁸F-alfatide PET/CT scans before CCRT and PET/CT parameters including maximum and mean standard uptake values (SUV_max/SUV_mean), peak standard uptake values (SUV_peak) and tumor volume (TV_PET and TV_CT) were obtained. The SUV_max of tumor and normal tissues (lung, blood pool and muscle) were measured, and their ratios were denoted as T/NT (T/NT_lung, T/NT_blood and T/NT_muscle). Statistical methods included the Two-example t test, Wilcoxon rank-sum test, Receiver-operating characteristic (ROC) curve analysis and logistic regression analyses.

Results

We found that SUV_max, SUV_peak, T/NT_lung, T/NT_blood and T/NT_muscle were higher in non-responders than in responders (P?=?0.0024, P?=?0.016, P?<?0.001, P?=?0.003, P?=?0.004). According to ROC curve analysis, the thresholds of SUV_max, SUV_peak, T/NT_lung, T/NT_blood and T/NT_muscle were 5.65, 4.46, 7.11, 5.41, and 11.75, respectively. The five parameters had high sensitivity, specificity and accuracy in distinguishing non-responders and responders. Multivariate logistic regression analyses showed that T/NT_lung was an independent predictor of the short-term outcome of CCRT in patients with advanced NSCLC (P?=?0.032).

Conclusions

¹⁸F-alfatide PET/CT may be useful in predicting the short-term outcome of CCRT in patients with advanced NSCLC.

     

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

Purpose

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

Methods

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

Results

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

Conclusion

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

     

Malignant lipogenesis defined by <Superscript>11</Superscript>C-acetate PET/CT predicts prostate cancer-specific survival in patients with biochemical relapse after prostatectomy

Purpose

Malignant de novo lipogenesis is strongly linked to the aggressiveness of prostate cancer (PCa) under experimental conditions. ¹¹C-Acetate PET/CT is a potential noninvasive biomarker of malignant lipogenesis in PCa, but its prognostic value is not known. The objective of this study was to analyse ¹¹C-acetate PET/CT image metrics in relation to survival.

Methods

All patients undergoing ¹¹C-acetate PET/CT in one university hospital from 2005 to 2011 due to PSA relapse after previous prostatectomy were retrospectively evaluated. Two groups of patients were compared: those who died from PCa and those who were censored. All previously reported findings of local recurrence, regional or distal lymph node metastases and bone metastases were counted and evaluated regarding ¹¹C-acetate uptake intensity (SUV_max) and tumour volume. Total tumour volume and total lipogenic activity (TLA, summed SUV_max × TV) were calculated. Survival analysis in the entire study population was followed by Cox proportional hazards ratio (HR) analysis.

Results

A total of 121 patients were included, and 22 PCa-specific deaths were recorded. The mean PSA level at the time of PET was 2.69?±?4.35 ng/mL. The median follow-up of the study population was 79?±?28 months. PET identified at least one PCa lesion in 53 % of patients. Five-year PCa-specific survival after PET was 80 % and 100 % in patients with a positive and a negative PET scan, respectively (p?<?0.001). Time-to-death was linearly correlated with highest SUV_max (r?=??0.55, p?=?0.01) and nonlinearly with TLA (r?=??0.75, p?<?0.001). Multivariate analysis showed statistical significance for number of bone metastases (HR 1.74, p?=?0.01), tertile of TLA (HR 5.63, p?=?0.029) and postoperative Gleason score (HR 1.84, p?=?0.045).

Conclusion

Malignant ¹¹C-acetate accumulation measured with PET/CT is a strong predictor of survival in the setting of PSA relapse after prostatectomy. The study provides further evidence for a quantitative relationship between malignant de novo lipogenesis and early death. ¹¹C-Acetate PET/CT might be useful for identifying a high-risk population of relapsing patients in which therapies targeting malignant lipogenesis might be of particular benefit.

     

SUV navigator enables rapid [<Superscript>18</Superscript>F]-FDG PET/CT image interpretation compared with 2D ROI and 3D VOI evaluations

Purpose

Positron emission tomography (PET) and the maximum standardized uptake value (SUV_max) is a useful technique for assessing malignant tumors. Measurements of SUV_max in multiple lesions per patient frequently require many time-consuming procedures. To address this issue, we designed a novel interface named SUV Navigator (SUVnavi), and the purpose of this study was to investigate its utility.

Materials and methods

We measured SUV_max in 661 lesions from 100 patients with malignant tumors. Diagnoses and SUV_max measurements were made with SUVnavi, 2D, and 3D measurements. SUV measurement accuracy in each method were also evaluated.

Results

The average reduction in time with SUVnavi versus 2D was 53.8% and 3D was 37.5%; time required with SUVnavi was significantly shorter than with 2D and 3D (P < 0.001 and P < 0.001, respectively). The time reduction and lesion number had a positive correlation (P < 0.001 and P < 0.001, respectively). SUV_max agreed with precise SUV_max in all lesions measured with SUVnavi and 3D but in only 466 of 661 lesions (70.5%) measured with 2D.

Conclusion

SUVnavi may be useful for rapid [¹⁸F]-fluorodeoxyglucose positron emission tomography/computed tomography ([¹⁸F]-FDG PET/CT) image interpretation without reducing the accuracy of SUV_max measurement.

     

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.

     

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>68</Superscript>Ga-PSMA PET/CT in the evaluation of bone metastases in prostate cancer

Purpose

The aims of this retrospective analysis were to compare ⁶⁸Ga-PSMA PET findings and low-dose CT findings (120 kV, 30 mA), and to obtain semiquantitative and quantitative ⁶⁸Ga-PSMA PET data in patients with prostate cancer (PC) bone metastases.

Methods

In total, 152 PET/CT scans from 140 patients were evaluated. Of these patients, 30 had previously untreated primary PC, and 110 had biochemical relapse after treatment of primary PC. All patients underwent dynamic PET/CT scanning of the pelvis and lower abdomen as well as whole-body PET/CT with ⁶⁸Ga-PSMA-11. The PET/CT scans were analysed qualitatively (visually), semiquantitatively (SUV), and quantitatively based on a two-tissue compartment model and a noncompartmental approach leading to the extraction of the fractal dimension. Differences were considered significant for p values <0.05.

Results

In total, 168 ⁶⁸Ga-PSMA-positive and 113 CT-positive skeletal lesions were detected in 37 patients (8 with primary PC, 29 with biochemical recurrence). Of these 168 lesions, 103 were both ⁶⁸Ga-PSMA PET-positive and CT-positive, 65 were only ⁶⁸Ga-PSMA-positive, and 10 were only CT-positive. The Yang test showed that there were significantly more ⁶⁸Ga-PSMA PET-positive lesions than CT-positive lesions. Association analysis showed that PSA plasma levels were significantly correlated with several ⁶⁸Ga-PSMA-11-associated parameters in bone metastases, including the degree of tracer uptake (SUV_average and SUV_max), its transport rate from plasma to the interstitial/intracellular compartment (K₁), its rate of binding to the PSMA receptor and its internalization (k₃), its influx rate (K_i), and its distribution heterogeneity.

Conclusion

⁶⁸Ga-PSMA PET/CT is a useful diagnostic tool in the detection of bone metastases in PC. ⁶⁸Ga-PSMA PET visualizes more bone metastases than low-dose CT. PSA plasma levels are significantly correlated with several ⁶⁸Ga-PSMA PET parameters.

     

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.