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.

     

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.

     

<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.

     

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.

     

Pulmonary <Superscript>18</Superscript>F-FDG uptake helps refine current risk stratification in idiopathic pulmonary fibrosis (IPF)

Purpose

There is a lack of prognostic biomarkers in idiopathic pulmonary fibrosis (IPF) patients. The objective of this study is to investigate the potential of ¹⁸F-FDG-PET/ CT to predict mortality in IPF.

Methods

A total of 113 IPF patients (93 males, 20 females, mean age?±?SD: 70?±?9 years) were prospectively recruited for ¹⁸F-FDG-PET/CT. The overall maximum pulmonary uptake of ¹⁸F-FDG (SUV_max), the minimum pulmonary uptake or background lung activity (SUV_min), and target-to-background (SUV_max/ SUV_min) ratio (TBR) were quantified using routine region-of-interest analysis. Kaplan–Meier analysis was used to identify associations of PET measurements with mortality. We also compared PET associations with IPF mortality with the established GAP (gender age and physiology) scoring system. Cox analysis assessed the independence of the significant PET measurement(s) from GAP score. We investigated synergisms between pulmonary ¹⁸F-FDG-PET measurements and GAP score for risk stratification in IPF patients.

Results

During a mean follow-up of 29 months, there were 54 deaths. The mean TBR?±?SD was 5.6?±?2.7. Mortality was associated with high pulmonary TBR (p?=?0.009), low forced vital capacity (FVC; p?=?0.001), low transfer factor (TLCO; p?<?0.001), high GAP index (p?=?0.003), and high GAP stage (p?=?0.003). Stepwise forward-Wald–Cox analysis revealed that the pulmonary TBR was independent of GAP classification (p?=?0.010). The median survival in IPF patients with a TBR < 4.9 was 71 months, whilst in those with TBR?> 4.9 was 24 months. Combining PET data with GAP data (“PET modified GAP score”) refined the ability to predict mortality.

Conclusions

A high pulmonary TBR is independently associated with increased risk of mortality in IPF patients.

     

<Superscript>68</Superscript>Ga-PSMA PET/CT Imaging Predicting Intraprostatic Tumor Extent,Extracapsular Extension and Seminal Vesicle Invasion Prior to Radical Prostatectomy in Patients with Prostate Cancer

Purpose

⁶⁸Ga-labeled prostate-specific membrane antigen (PSMA) ligand positron emission tomography/computed tomography (PET/CT) has shown promising results in patients with biochemical recurrence after primary therapy for prostate cancer. In this study, we evaluated the usefulness of PSMA I&T (imaging and therapy) PET/CT prior to radical prostatectomy.

Methods

The study population consisted of 21 patients with prostate cancer who underwent ⁶⁸Ga-PSMA I&T PET/CT before either open or laparoscopic radical prostatectomy. Intraprostatic tumor extent, extracapsular extension (ECE) and seminal vesicle invasion (SVI) were assessed on the PET/CT scans. Tracer uptake was quantified in terms of standardized uptake values (SUVs). Imaging findings were correlated with final whole-gland histopathology.

Results

Of the 21 patients, two had T stage 2b disease, nine stage 2c, six stage 3a and four stage 3b. The median Gleason score was 7. The SUV_mean of the primary tumors was 9.5?±?8.8. SUV_mean was higher in tumors with ECE than in organ-confined tumors (13.8?±?11.0 vs. 5.6?±?3.2, p?=?0.029). Peak tracer uptake was significantly positively correlated with Gleason score (r _s?=?0.49, p?=?0.025). Sensitivity, specificity, positive predictive value and negative predictive value were, respectively, 94.7%, 75.0%, 97.3% and 60.0% for tumor infiltration of an individual prostate lobe, 75.0%, 100.0%, 100.0% and 97.4% for SVI, and 90.0%, 90.9%, 90.0% and 90.9% for ECE, using an angulated contour of the prostate as the criterion. Tumor volume derived from ⁶⁸Ga-PSMA I&T PET/CT was significantly correlated with preoperative prostate-specific antigen value (r _p?=?0.75, p?<?0.001) and tumor volume on histopathology (r _p?=?0.45, p?=?0.039).

Conclusions

⁶⁸Ga-PSMA I&T PET/CT prior to radical prostatectomy can contribute to presurgical local staging of prostate cancer. In this pilot study, ⁶⁸Ga-PSMA I&T PET/CT showed promising results for prediction of lobe infiltration, ECE and SVI.

     

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.

     

Prognostic Value of Tumor-to-Blood Standardized Uptake Ratio in Patients with Resectable Non-Small-Cell Lung Cancer

Objectives

Previously published studies showed that the standard tumor-to-blood standardized uptake value (SUV) ratio (SUR) was a more accurate prognostic method than tumor maximum standardized uptake value (SUV_max). This study evaluated and compared prognostic value of positron emission tomography (PET) parameters and normalized value of PET parameters by blood pool SUV in non-small-cell lung cancer (NSCLC) patients who received curative surgery.

Methods

Seventy-seven patients who underwent curative resection for NSCLC between January 2010 to December 2013 were enrolled in this study. ¹⁸Fluorine-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) was performed before surgery. The mean standardized uptake value (SUV_mean), SUV_max, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of each lesion was measured, on the workstation. SUR_mean, SUR_max, and TLGSUR were calculated by dividing each of them by descending aorta SUV_mean. Cox proportional hazards regression was used to analyze the effect of age, sex, pathological parameters, and PET parameters on recurrence and death.

Results

In Cox regression analysis, N stage predicted for both recurrence (p?<?0.0001) and death (p?<?0.0001). SUR_max predicted recurrence (p?=?0.0014), not death. Area under the receiver operating characteristic curve of SUR_max was 0.759 with cutoff value 4.004. However, SUV_max, SUV_mean, MTV, TLG, SUR_mean, and TLGSUR predicted neither recurrence nor death.

Conclusions

Among PET parameters, SUR_max was the independent predictor of recurrence in NSCLC patients who received curative surgery. N stage was the independent prognostic factor for both recurrence and death. Both parameters could be used to stratify the risk of NSCLC patients.

     

<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.

     

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.

     

Prognostic value of FDG-PET and DWI in breast cancer

Objective

To investigate the prognostic value of preoperative FDG-PET/CT and diffusion weighted imaging (DWI) in patients with breast cancer.

Methods

A total of 73 patients with newly diagnosed invasive breast cancer who had undergone preoperative whole-body FDG-PET/CT and 3-Tesla breast MRI including DWI followed by surgery were identified. Effects of primary tumor PET parameters [maximum standardized uptake value (SUV_max), mean SUV (SUV_mean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] and DWI parameters [mean apparent diffusion coefficient (ADC_mean) and minimum ADC (ADC_min)] including clinicopathologic factors on disease-free survival (DFS) were retrospectively evaluated using the log-rank and Cox methods.

Results

After a median overall follow-up of 32.3 months in all patients, 6 (8.2%) of the 73 patients had recurrence. Receiver operating characteristic curve analysis and log-rank tests showed that patients with a high primary tumor SUV_max (≥?3.60), MTV (≥?3.15), and TLG (≥?16.0) had a significantly lower DFS rate than those with a low SUV_max (<?3.60), MTV (<?3.15), and TLG (<?16.0), respectively (p?=?0.0054, p?=?0.0054, and p?<?0.0001, respectively). SUV_mean, ADC_mean, and ADC_min were not significantly associated with recurrence. Univariate analysis showed that SUV_max (p?=?0.0054), MTV (p?=?0.0054), TLG (p?<?0.0001), tumor size (p?=?0.0083), estrogen receptor negativity (p?=?0.046), progesterone receptor negativity (p?=?0.0023), human epidermal growth factor receptor 2 positivity (p?=?0.043), and the presence of axillary lymph node metastasis (p?=?0.0037) were also significantly associated with recurrence. However, in multivariate analysis, none of them were an independent factor.

Conclusions

The preoperative SUV_max, MTV, and TLG of primary breast cancer are prognostic factors for recurrence, whereas ADC values are not.

     

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.

     

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.

     

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.

     

Prognostic value of [<Superscript>18</Superscript>F]FDG-PET/CT in multiple myeloma patients before and after allogeneic hematopoietic cell transplantation

Purpose

Despite improved treatment options, multiple myeloma (MM) remains an incurable disease. The aim of this study was to investigate the prognostic value of positron emission tomography/computed tomography (PET/CT) using ¹⁸F-2’-deoxy-2’-fluorodeoxyglucose ([¹⁸F]FDG) in MM patients shortly before and ~100 days after allogeneic hematopoietic cell transplantation (allo-HCT).

Methods

In this retrospective analysis, we evaluated [¹⁸F]FDG-PET/CT-scans of 45 heavily pre-treated MM patients before and 27 patients after scheduled allo-HCT. All scans were qualitatively and semi-quantitatively assessed for the presence of active disease. Serological response was recorded according to International Myeloma Working Group (IMWG) criteria. Progression-free (PFS) and overall survival (OS) were correlated with different PET/CT-derived parameters, such as presence, number and maximum standardized uptake value (SUV_max) of focal myeloma lesions. The impact of extramedullary disease on patient outcome was also assessed.

Results

PET/CT negativity -prior to or following allo-HCT- was a favorable prognostic factor for progression-free and overall survival (both, PFS and OS: pre-HSCT p?<?0.001, post-HCT p?<?0.005). High FDG-uptake (SUV_max?>?6.5) revealed a significantly shortened survival compared to patients with a lower SUV_max (<6.5) (OS, 5.0?±?1.1 m vs. not reached - longest 122.0 m; p?<?0.001). Moreover, our data prove that a higher number (>3) of focal lesions (pre-HCT: both PFS and OS: p?<?0.001; post-HCT PFS: p?<?0.001, OS: p?=?0.139) as well as the presence of extramedullary disease serve as adverse prognostic factors prior to and after allo-HCT. At response assessment after allo-HCT, [¹⁸F]FDG-PET/CT had a complementary value in prognostication in addition to IMWG criteria alone.

Conclusion

[¹⁸F]FDG-PET/CT before and shortly after allogeneic HCT is a powerful predictor for progression-free and overall survival in MM patients.

     

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.

     

[<Superscript>18</Superscript>F]FDG PET accurately differentiates infected and non-infected non-unions after fracture fixation

Purpose

Complete fracture healing is crucial for good patient outcomes. A major complication in the treatment of fractures is non-union. The pathogenesis of non-unions is not always clear, although implant-associated infections play a significant role, especially after surgical treatment of open fractures. We aimed to evaluate the value of [¹⁸F]FDG PET in suspected infections of non-union fractures.

Methods

We retrospectively evaluated 35 consecutive patients seen between 2000 and 2015 with suspected infection of non-union fractures, treated at a level I trauma center. The patients underwent either [¹⁸F]FDG PET/CT (N?=?24), [¹⁸F]FDG PET (N?=?11) plus additional CT (N?=?8), or conventional X-ray (N?=?3). Imaging findings were correlated with final diagnosis based on intraoperative culture or follow-up.

Results

In 13 of 35 patients (37 %), infection was proven by either positive intraoperative tissue culture (N?=?12) or positive follow-up (N?=?1). [¹⁸F]FDG PET revealed 11 true-positive, 19 true-negative, three false-positive, and two false-negative results, indicating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 85 %, 86 %, 79 %, 90 %, and 86 %, respectively. The SUV_max was 6.4?±?2.7 in the clinically infected group and 3.0?±?1.7 in the clinically non-infected group (p <0.01). The SUV_ratio was 5.3?±?3.3 in the clinically infected group and 2.6?±?1.5 in the clinically non-infected group (p <0.01).

Conclusion

[¹⁸F]FDG PET differentiates infected from non-infected non-unions with high accuracy in patients with suspected infections of non-union fractures, for whom other clinical findings were inconclusive for a local infection. [¹⁸F]FDG PET should be considered for therapeutic management of non-unions.

     

The value of <Superscript>18</Superscript>F-FDG PET before and after induction chemotherapy for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy in oesophageal adenocarcinoma

Purpose

The purpose of our study was to determine the value of ¹⁸F-FDG PET before and after induction chemotherapy in patients with oesophageal adenocarcinoma for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy (CRT).

Methods

In 70 consecutive patients receiving a three-step treatment strategy of induction chemotherapy and preoperative chemoradiotherapy for oesophageal adenocarcinoma, ¹⁸F-FDG PET scans were performed before and after induction chemotherapy (before preoperative CRT). SUV_max, SUV_mean, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were determined at these two time points. The predictive potential of (the change in) these parameters for a poor pathologic response, progression-free survival (PFS) and overall survival (OS) was assessed.

Results

A poor pathologic response after induction chemotherapy and preoperative CRT was found in 27 patients (39 %). Patients with a poor pathologic response experienced less of a reduction in TLG after induction chemotherapy (p?<?0.01). The change in TLG was predictive for a poor pathologic response at a threshold of ?26 % (sensitivity 67 %, specificity 84 %, accuracy 77 %, PPV 72 %, NPV 80 %), yielding an area-under-the-curve of 0.74 in ROC analysis. Also, patients with a decrease in TLG lower than 26 % had a significantly worse PFS (p?=?0.02), but not OS (p?=?0.18).

Conclusions

¹⁸F-FDG PET appears useful to predict a poor pathologic response as well as PFS early after induction chemotherapy in patients with oesophageal adenocarcinoma undergoing a three-step treatment strategy. As such, the early ¹⁸F-FDG PET response after induction chemotherapy could aid in individualizing treatment by modification or withdrawal of subsequent preoperative CRT in poor responders.

     

Prospective evaluation of [<Superscript>11</Superscript>C]Choline PET/CT in therapy response assessment of standardized docetaxel first-line chemotherapy in patients with advanced castration refractory prostate cancer

Purpose

The aim of this study was to prospectively evaluate the value of [¹¹C] Choline PET/CT in monitoring early and late response to a standardized first-line docetaxel chemotherapy in castration refractory prostate cancer (mCRPC) patients.

Methods

Thirty-two patients were referred for [¹¹C] Choline PET/CT before the start of docetaxel chemotherapy, after one and ten chemotherapy cycles (or - in case of discontinuation - after the last administered cycle) for therapy response assessment. [¹¹C] Choline uptake (SUV_max, SUV_mean), CT derived Houndsfield units (HU_max, HU_mean), and volume of bone, lung, and nodal metastases and local recurrence were measured semi-automatically at these timepoints. Change in SUV_max, SUV_mean, HU_max, HU_mean, and volume was assessed between PET 2 and 1 (early response assessment, ERA) and PET 3 and 1 (late response assessment, LRA) on a patient and lesion basis. Results of PET/CT were compared to clinically used RECIST 1.1 and clinical criteria based therapy response assessment including PSA for defining progressive disease (PD) and non-progressive disease (nPD), respectively. Relationships between changes of SUV_max and SUV_mean (early and late) and changes of PSA_early and PSA_late were evaluated. Prognostic value of initial SUV_max and SUV_mean was assessed. Statistical analyses were performed using SPSS.

Results

In the patient-based ERA and LRA there were no statistically significant differences in change of choline uptake, HU, and volume between PD and nPD applying RECIST or clinical response criteria. In the lesion-based ERA, decrease in choline uptake of bone metastases was even higher in PD (applying RECIST criteria), whereas in LRA the decrease was higher in nPD (applying clinical criteria). There were only significant correlations between change in choline uptake and PSA in ERA in PD, in LRA no significant correlations were discovered. Initial SUV_max and SUV_mean were statistically significantly higher in nPD (applying clinical criteria).

Conclusion

There is no significant correlation between change in choline uptake in [¹¹C] Choline PET/CT and clinically routinely used objective response assessment during the early and late course of docetaxel chemotherapy. Therefore, [¹¹C] Choline PET/CT seems to be of limited use in therapy response assessment in standardized first-line chemotherapy in mCRPC patients.

     

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.