Heterogeneity index evaluated by slope of linear regression on <Superscript>18</Superscript>F-FDG PET/CT as a prognostic marker for predicting tumor recurrence in pancreatic ductal adenocarcinoma

Purpose

¹⁸F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) has been investigated as a method to predict pancreatic cancer recurrence after pancreatic surgery. We evaluated the recently introduced heterogeneity indices of ¹⁸F-FDG PET/CT used for predicting pancreatic cancer recurrence after surgery and compared them with current clinicopathologic and ¹⁸F-FDG PET/CT parameters.

Methods

A total of 93 pancreatic ductal adenocarcinoma patients (M:F = 60:33, mean age = 64.2 ± 9.1 years) who underwent preoperative ¹⁸F-FDG PET/CT following pancreatic surgery were retrospectively enrolled. The standardized uptake values (SUVs) and tumor-to-background ratios (TBR) were measured on each ¹⁸F-FDG PET/CT, as metabolic parameters. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were examined as volumetric parameters. The coefficient of variance (heterogeneity index-1; SUVmean divided by the standard deviation) and linear regression slopes (heterogeneity index-2) of the MTV, according to SUV thresholds of 2.0, 2.5 and 3.0, were evaluated as heterogeneity indices. Predictive values of clinicopathologic and ¹⁸F-FDG PET/CT parameters and heterogeneity indices were compared in terms of pancreatic cancer recurrence.

Results

Seventy patients (75.3%) showed recurrence after pancreatic cancer surgery (mean recurrence = 9.4 ± 8.4 months). Comparing the recurrence and no recurrence patients, all of the ¹⁸F-FDG PET/CT parameters and heterogeneity indices demonstrated significant differences. In univariate Cox-regression analyses, MTV (P = 0.013), TLG (P = 0.007), and heterogeneity index-2 (P = 0.027) were significant. Among the clinicopathologic parameters, CA19–9 (P = 0.025) and venous invasion (P = 0.002) were selected as significant parameters. In multivariate Cox-regression analyses, MTV (P = 0.005), TLG (P = 0.004), and heterogeneity index-2 (P = 0.016) with venous invasion (P < 0.001, 0.001, and 0.001, respectively) demonstrated significant results.

Conclusions

The heterogeneity index obtained using the linear regression slope, could be an effective predictor of pancreatic cancer recurrence after pancreatic cancer surgery, in addition to ¹⁸F-FDG PET/CT volumetric parameters and clinicopathologic parameters.

     

Preliminary feasibility study on differential diagnosis between radiation-induced cerebral necrosis and recurrent brain tumor by means of [<Superscript>18</Superscript>F]fluoro-borono-phenylalanine PET/CT

Objectives

A previous study reported that a differential diagnosis between glioblastoma progression and radiation necrosis by 4-borono-2-[¹⁸F]-fluoro-phenylalanine ([¹⁸F]FBPA) PET can be made based on lesion-to-normal ratio of [¹⁸F]FBPA accumulation. Two-dimensional data acquisition mode PET alone system, with in-plane resolution of 7.9 mm and axial resolution of 13.9 mm, was used. In the current study, we aimed to confirm the differential diagnostic capability of [¹⁸F]FBPA PET/CT with higher PET spatial resolution by three-dimensional visual inspection and by measuring mean standardized uptake value (SUVmean), maximum SUV (SUVmax), metabolic tumor volume (MTV), and total lesion (TL) [¹⁸F]FBPA uptake.

Methods

Twelve patients of glioma (9), malignant meningioma (1), hemangiopericytoma (1), and metastatic brain tumor (1) were enrolled. All had preceding radiotherapy. High-resolution three-dimensional data acquisition mode PET/CT with in-plane resolution of 4.07 mm and axial resolution of 5.41 mm was employed for imaging. Images were three-dimensionally analyzed using the PMOD software. SUVmean and SUVmax of lesion and normal brain were measured. Lesion MTV and TL FBPA uptake were calculated. The diagnostic accuracy of [¹⁸F]FBPA PET/CT in detecting recurrence (n?=?6) or necrosis (n?=?6) was verified by clinical follow-up.

Results

All parameters showed significantly higher values for tumor recurrence than for necrosis. SUVmean in recurrence was 2.95?±?0.84 vs 1.18?±?0.24 in necrosis (P?=?0.014); SUVmax in recurrence was 4.63?±?1.23 vs 1.93?±?0.44 in necrosis (P?=?0.014); MTV in recurrence was 44.92?±?28.93 mL vs 10.66?±?8.46 mL in necrosis (P?=?0.032); and mean TL FBPA uptake in recurrence was 121.01?±?50.48 g vs 12.36?±?9.70 g in necrosis (P?=?0.0029).

Conclusion

In this preliminary feasibility study, we confirmed the possibility of differentiating tumor recurrence from radiation necrosis in patients with irradiated brain tumors by [¹⁸F]FBPA PET/CT using indices of SUVmean, SUVmax, MTV, and TL ¹⁸FBPA uptake.

     

Prospective comparison of <Superscript>68</Superscript>Ga-DOTATATE and <Superscript>18</Superscript>F-FDOPA PET/CT in patients with various pheochromocytomas and paragangliomas with emphasis on sporadic cases

Purpose

Pheochromocytomas/paragangliomas (PHEOs/PGLs) overexpress somatostatin receptors and recent studies have already shown excellent results in the localization of these tumors using ⁶⁸Ga-labeled somatostatin analogs (⁶⁸Ga-DOTA-SSA), especially in patients with germline succinate dehydrogenase subunit B gene (SDHB) mutations and head and neck PGLs (HNPGLs). The value of ⁶⁸Ga-DOTA-SSA has to be established in sporadic cases, including PHEOs. Thus, the aim of this study was to compare ⁶⁸Ga-DOTATATE PET/CT, ¹⁸F-FDOPA PET/CT, and conventional imaging in patients with various PHEOs/PGLs with a special emphasis on sporadic cases, including those located in the adrenal gland.

Design

⁶⁸Ga-DOTATATE, ¹⁸F-FDOPA PET/CT, and conventional imaging (contrast-enhanced CT and MRI with MR angiography sequences) were prospectively performed in 30 patients (8 with SDHD mutations, 1 with a MAX mutation and 21 sporadic cases) with PHEO/PGL at initial diagnosis or relapse.

Results

The patient-based sensitivities were 93 % (28/30), 97 % (29/30), and 93 % (28/30) for ⁶⁸Ga-DOTATATE PET/CT, ¹⁸F-FDOPA PET/CT, and conventional imaging, respectively. The lesion-based sensitivities were 93 % (43/46), 89 % (41/46), and 76 % (35/46) for ⁶⁸Ga-DOTATATE PET/CT, ¹⁸F-FDOPA PET/CT, and conventional imaging respectively (p?=?0.042). ⁶⁸Ga-DOTATATE PET/CT detected a higher number of HNPGLs (30/30) than ¹⁸F-FDOPA PET/CT (26/30; p?=?0.112) and conventional imaging (24/30; p?=?0.024). ⁶⁸Ga-DOTATATE PET/CT missed two PHEOs of a few millimeters in size and a large recurrent PHEO. One lesion was considered false-positive on ⁶⁸Ga-DOTATATE PET/CT and corresponded to a typical focal lesion of fibrous dysplasia on MRI. Among the 11 lesions missed by conventional imaging, 7 were detected by conventional imaging with knowledge of the PET results (4 HNPGLs, 2 LNs, and 1 recurrent PHEO).

Conclusion

⁶⁸Ga-DOTATATE PET/CT is the most sensitive tool in the detection of HNPGLs, especially SDHD-related tumors, which may be very small and fail to concentrate sufficient ¹⁸F-FDOPA. The present study further expands the use of ⁶⁸Ga-DOTATATE for all patients with HNPGLs, regardless of their genotype. ⁶⁸Ga-DOTATATE PET/CT may be inferior to ¹⁸F-FDOPA PET/CT in the detection PHEOs.

     

<Superscript>11</Superscript>C-methylaminoisobutyric acid (MeAIB) PET for evaluation of prostate cancer: compared with <Superscript>18</Superscript>F-fluorodeoxyglucose PET

Objective

α-N-methyl-¹¹C-methylaminoisobutyric acid (¹¹C-MeAIB) is a selective substrate of system A amino acid transport, and known to accumulate in malignant lesions. The aim of this study was to evaluate the utility of MeAIB PET for the assessment of prostate cancer, compared with FDG PET.

Methods

Thirty-four men (age range 57–77 years) with prostate cancer were prospectively enrolled, and underwent MeAIB PET and FDG PET between January 2011 and January 2013. MeAIB PET and FDG PET were performed at 20 and 50 min post-injection, respectively. SUVmax of the prostate was calculated, and visual analysis was conducted for MeAIB and FDG PET studies. MRI images were visually evaluated if available. All patients received total prostatectomy subsequently, and imaging findings were compared with pathological results, including T stage, Gleason score, and tumor size. The patient-based and lesion-based sensitivity and specificity were calculated according to pathological significant cancer.

Results

Mean value of SUVmax of ¹¹C-MeAIB PET and ¹⁸F-FDG PET in prostate cancer were 3.18 (±1.90, range; 1.55–9.57) and 3.88 (±2.85, range; 2.04–14.47). MeAIB PET and FDG PET were positive by visual analysis in 47.1 % (16/34) and 44.1 % (15/34) of the patients. MRI was positive in 51.5 % (17/33). Pathological stage and Gleason score were as follows: Stage 2 (n = 23), 3 (n = 8), and 4 (n = 3); Gleason score 6 (n = 13), 7 (n = 16), 8 (n = 3), and 9 (n = 2). The sensitivities tended to be higher according to higher pathological T stage or Gleason sum score for both MeAIB and FDG PET studies. Visual analysis of both MeAIB PET and FDG PET had significant correlation with extraprostatic extension (p < 0.05). MeAIB PET and FDG PET had complementary results by visual analysis in the assessment of prostate cancer. The patient-based sensitivity of MeAIB PET, FDG PET, and MRI were 51.6, 48.4, and 56.7 %, respectively. The patient-based specificity of these modalities was 100 % for each modality.

Conclusions

MeAIB PET has better diagnostic results than FDG PET for the assessment of significant prostate cancer, and these PET studies showed complementary results. MRI has even better diagnostic results than ¹¹C-MeAIB PET. MeAIB accumulates in prostate cancer, which indicates that the system A amino acid transport pathway is activated in prostate cancer.

     

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.

     

The value of [<Superscript>11</Superscript>C]-acetate PET and [<Superscript>18</Superscript>F]-FDG PET in hepatocellular carcinoma before and after treatment with transarterial chemoembolization and bevacizumab

Purpose

This prospective study was to investigate the value of [¹¹C]-acetate PET and [¹⁸F]-FDG PET in the evaluation of hepatocellular carcinoma (HCC) before and after treatment with transarterial chemoembolization (TACE) and vascular endothelial growth factor (VEGF) antibody (bevacizumab).

Methods

Twenty-two patients (three women, 19 men; 62 ± 8 years) with HCC verified by histopathology were treated with TACE and bevacizumab (n = 11) or placebo (n = 11). [¹¹C]-acetate PET and [¹⁸F]-FDG PET were performed before and after TACE with bevacizumab or placebo. Comparisons between groups were performed with t-tests and Chi-squared tests, where appropriate. Overall survival (OS) was defined as the time from start of bevacizumab or placebo until the date of death/last follow-up, respectively.

Results

The patient-related sensitivity of [¹¹C]-acetate PET, [¹⁸F]-FDG PET, and combined [¹¹C]-acetate and [¹⁸F]-FDG PET was 68%, 45%, and 73%, respectively. There was a significantly higher rate of conversion from [¹¹C]-acetate positive lesions to negative lesions in patients treated with TACE and bevacizumab as compared with that in patients with TACE and placebo (p < 0.05). In patients with negative acetate PET, the mean OS in patients treated with TACE and bevacizumab was 259 ± 118 days and was markedly shorter as compared with that (668 ± 217 days) in patients treated with TACE and placebo (p < 0.05). In patients treated with TACE and placebo, there was significant difference in mean OS in patients with positive FDG PET as compared with that in patients with negative FDG PET (p < 0.05). The HCC lesions had different tracer avidities showing the heterogeneity of HCC.

Conclusions

Our study suggests that combining [¹⁸F]-FDG with [¹¹C]-acetate PET could be useful for the management of HCC patients and might also provide relevant prognostic and molecular heterogeneity information.

     

[<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.

     

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.

     

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.

     

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.

     

Ability of <Superscript>18</Superscript>F-DOPA PET/CT and fused <Superscript>18</Superscript>F-DOPA PET/MRI to assess striatal involvement in paediatric glioma

Purpose

To assess the diagnostic performance of ¹⁸F-DOPA PET/CT and fused ¹⁸F-DOPA PET/MRI in detecting striatal involvement in children with gliomas.

Methods

This retrospective study included 28 paediatric patients referred to our institution for the presence of primary, residual or recurrent glioma (12 boys, 16 girls; mean age 10.7 years) and investigated with ¹⁸F-DOPA PET/CT and brain MRI. Fused ¹⁸F-DOPA PET/MR images were obtained and compared with PET/CT and MRI images. Accuracy, sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) for striatal involvement were calculated for each diagnostic tool. Univariate and multivariate logistic analyses were applied to evaluate the associations between ¹⁸F-DOPA PET/CT and fused ¹⁸F-DOPA PET/MRI diagnostic results and tumour uptake outside the striatum, grade, dimension and site of striatal involvement (ventral and/or dorsal).

Results

Accuracy, sensitivity, specificity, PPV, and NPV were 100 % for MRI, 93 %, 89 %, 100 %, 100 % and 82 % for ¹⁸F-DOPA PET/MRI, and 75 %, 74 %, 78 %, 88 % and 58 % for ¹⁸F-DOPA PET/CT, respectively. ¹⁸F-DOPA PET/MRI showed a trend towards higher accuracy compared with ¹⁸F-DOPA PET/CT (p?=?0.06). MRI showed significantly higher accuracy compared with ¹⁸F-DOPA PET/CT (p?=?0.01), but there was no significant difference between MRI and ¹⁸F-DOPA PET/MRI. Both univariate and multivariate logistic analyses showed a significant association (OR 8.0 and 7.7, respectively) between the tumour-to-normal striatal uptake (T/S) ratio and the diagnostic ability of ¹⁸F-DOPA PET/CT (p?=?0.03). A strong significant association was also found between involvement of the dorsal striatum and the ¹⁸F-DOPA PET/CT results (p?=?0.001), with a perfect prediction of involvement of the dorsal striatum by ¹⁸F-DOPA PET/MRI.

Conclusion

Physiological striatal ¹⁸F-DOPA uptake does not appear to be a main limitation in the evaluation of basal ganglia involvement.¹⁸F-DOPA PET/CT correctly detected involvement of the dorsal striatum in lesions with a T/S ratio >1, but appeared to be less suitable for evaluation of the ventral striatum. The use of fused ¹⁸F-DOPA PET/MRI further improves the accuracy and is essential for evaluation of the ventral striatum.

     

Prediction of breast cancer recurrence using lymph node metabolic and volumetric parameters from <Superscript>18</Superscript>F-FDG PET/CT in operable triple-negative breast cancer

Purpose

Triple-negative breast cancer has a poor prognosis. We evaluated several metabolic and volumetric parameters from preoperative ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in the prognosis of triple-negative breast cancer and compared them with current clinicopathologic parameters.

Methods

A total of 228 patients with triple-negative breast cancer (mean age 47.0 ± 10.8 years, all women) who had undergone preoperative PET/CT were included. The PET/CT metabolic parameters evaluated included maximum, peak, and mean standardized uptake values (SUVmax, SUVpeak, and SUVmean, respectively). The volumetric parameters evaluated included metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Metabolic and volumetric parameters were evaluated separately for tumor (T) and lymph nodes (N). The prognostic value of these parameters was compared with that of clinicopathologic parameters.

Results

All lymph node metabolic and volumetric parameters showed significant differences between patients with and without recurrence. However, tumor metabolic and volumetric parameters showed no significant differences. In a univariate survival analysis, all lymph node metabolic and volumetric parameters (SUVmax-N, SUVpeak-N, SUVmean-N, MTV-N, and TLG-N; all P < 0.001), T stage (P = 0.010), N stage (P < 0.001), and TNM stage (P < 0.001) were significant parameters. In a multivariate survival analysis, SUVmax-N (P = 0.005), MTV (P = 0.008), and TLG (P = 0.006) with TNM stage (all P < 0.001) were significant parameters.

Conclusions

Lymph node metabolic and volumetric parameters were significant predictors of recurrence in patients with triple-negative breast cancer after surgery. Lymph node metabolic and volumetric parameters were useful parameters for evaluating prognosis in patients with triple-negative breast cancer by ¹⁸F-FDG PET/CT, rather than tumor parameters.

     

<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.

     

Automatic calculation of myocardial external efficiency using a single <Superscript>11</Superscript>C-acetate PET scan

Background

Myocardial external efficiency (MEE) is defined as the ratio of kinetic energy associated with cardiac work [forward cardiac output (FCO)*mean systemic pressure] and the chemical energy from oxygen consumed (MVO₂) by the left ventricular mass (LVM). We developed a fully automated method for estimating MEE based on a single ¹¹C-acetate PET scan without ECG-gating.

Methods and Results

Ten healthy controls, 34 patients with aortic valve stenosis (AVS), and 20 patients with mitral valve regurgitation (MVR) were recruited in a dual-center study. MVO₂ was calculated using washout of ¹¹C -acetate activity. FCO and LVM were calculated automatically using dynamic PET and parametric image formation. FCO and LVM were also obtained using cardiac magnetic resonance (CMR) in all subjects. The correlation between MEE_PET-CMR and MEE_PET was high (r = 0.85, P < 0.001) without significant bias. MEE_PET was 23.6 ± 4.2% for controls and was lowered in AVS (17.2 ± 4.3%, P < 0.001) and in MVR (18.0 ± 5.2%, P = 0.004). MEE_PET was strongly associated with both NYHA class (P < 0.001) and the magnitude of valvular dysfunction (mean aortic gradient: P < 0.001, regurgitant fraction: P = 0.009).

Conclusion

A single ¹¹C-acetate PET yields accurate and automated MEE results on different scanners. MEE might provide an unbiased measurement of the phenotypic response to valvular disease.

     

Evaluation of ECG-gated [<Superscript>11</Superscript>C]acetate PET for measuring left ventricular volumes,mass, and myocardial external efficiency

Background

Noninvasive estimation of myocardial external efficiency (MEE) requires measurements of left ventricular (LV) oxygen consumption with [¹¹C]acetate PET in addition to LV stroke volume and mass with cardiovascular magnetic resonance (CMR). Measuring LV geometry directly from ECG-gated [¹¹C]acetate PET might enable MEE evaluation from a single PET scan. Therefore, we sought to establish the accuracy of measuring LV volumes, mass, and MEE directly from ECG-gated [¹¹C]acetate PET.

Methods

Thirty-five subjects with aortic valve stenosis underwent ECG-gated [¹¹C]acetate PET and CMR. List mode PET data were rebinned into 16-bin ECG-gated uptake images before measuring LV volumes and mass using commercial software and compared to CMR. Dynamic datasets were used for calculation of mean LV oxygen consumption and MEE.

Results

LV mass, volumes, and ejection fraction measured by CMR and PET correlated strongly (r = 0.86-0.92, P < .001 for all), but were underestimated by PET (P < .001 for all except ESV P = .79). PET-based MEE, corrected for bias, correlated fairly with PET/CMR-based MEE (r = 0.60, P < .001, bias ?3 ± 21%, P = .56). PET-based MEE bias was strongly associated with LV wall thickness.

Conclusions

Although analysis-related improvements in accuracy are recommended, LV geometry estimated from ECG-gated [¹¹C]acetate PET correlate excellently with CMR and can indeed be used to evaluate MEE.

     

<Superscript>11</Superscript>C-L-methyl methionine dynamic PET/CT of skeletal muscle: response to protein supplementation compared to L-[ring <Superscript>13</Superscript>C<Subscript>6</Subscript>] phenylalanine infusion with serial muscle biopsy

Objective

The objective of this study was to determine if clinical dynamic PET/CT imaging with ¹¹C-L-methyl-methionine (¹¹C-MET) in healthy older women can provide an estimate of tissue-level post-absorptive and post-prandial skeletal muscle protein synthesis that is consistent with the more traditional method of calculating fractional synthesis rate (FSR) of muscle protein synthesis from skeletal muscle biopsies obtained during an infusion of L-[ring ¹³C₆] phenylalanine (¹³C₆-Phe).

Methods

Healthy older women (73?±?5 years) completed both dynamic PET/CT imaging with ¹¹C-MET and a stable isotope infusion of ¹³C₆-Phe with biopsies to measure the skeletal muscle protein synthetic response to 25 g of a whey protein supplement. Graphical estimation of the Patlak coefficient K_i from analysis of the dynamic PET/CT images was employed as a measure of incorporation of 11 C-MET in the mid-thigh muscle bundle.

Results

Post-prandial values [mean?±?standard error of the mean (SEM)] were higher than post-absorptive values for both K_i (0.0095?±?0.001 vs. 0.00785?±?0.001 min^?1, p?<?0.05) and FSR (0.083?±?0.008 vs. 0.049?±?0.006%/h, p?<?0.001) in response to the whey protein supplement. The percent increase in K_i and FSR in response to the whey protein supplement was significantly correlated (r?=?0.79, p?=?0.015).

Conclusions

Dynamic PET/CT imaging with ¹¹C-MET provides an estimate of the post-prandial anabolic response that is consistent with a traditional, invasive stable isotope, and muscle biopsy approach. These results support the potential future use of ¹¹C-MET imaging as a non-invasive method for assessing conditions affecting skeletal muscle protein synthesis.

     

<Superscript>18</Superscript>F-FPYBF-2, a new F-18-labelled amyloid imaging PET tracer: first experience in 61 volunteers and 55 patients with dementia

Objective

Recently, we developed a benzofuran derivative for the imaging of β-amyloid plaques, 5-(5-(2-(2-(2-¹⁸F-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)-N-methylpyridin-2-amine (¹⁸F-FPYBF-2) (Ono et al., J Med Chem 54:2971–9, 2011). The aim of this study was to assess the feasibility of ¹⁸F-FPYBF-2 as an amyloid imaging PET tracer in a first clinical study with healthy volunteers and patients with various dementia and in comparative dual tracer study using ¹¹C-Pittsburgh Compound B (¹¹C-PiB).

Methods

61 healthy volunteers (age: 53.7?±?13.1 years old; 19 male and 42 female; age range 24–79) and 55 patients with suspected dementia [Alzheimer’s Disease (AD); early AD: n?=?19 and moderate stage AD: n?=?8, other dementia: n?=?9, mild cognitive impairment (MCI): n?=?16, cognitively normal: n?=?3] for first clinical study underwent static head PET/CT scan using ¹⁸ F ^? FPYBF-2 at 50–70 min after injection. 13 volunteers and 14 patients also underwent dynamic PET scan at 0–50 min at the same instant. 16 subjects (volunteers: n?=?5, patients with dementia: n?=?11) (age: 66.3?±?14.2 years old; 10 males and 6 females) were evaluated for comparative study (50–70 min after injection) using ¹⁸F-FPYBF-2 and ¹¹C-PiB on separate days, respectively. Quantitative analysis of mean cortical uptake was calculated using Mean Cortical Index of SUVR (standardized uptake value ratio) based on the established method for ¹¹C-PiB analysis using cerebellar cortex as control.

Results

Studies with healthy volunteers showed that ¹⁸F-FPYBF-2 uptake was mainly observed in cerebral white matter and that average Mean Cortical Index at 50–70 min was low and stable (1.066?±?0.069) basically independent from age or gender. In patients with AD, ¹⁸F-FPYBF-2 uptake was observed both in cerebral white and gray matter, and Mean Cortical Index was significantly higher (early AD: 1.288?±?0.134, moderate AD: 1.342?±?0.191) than those of volunteers and other dementia (1.018?±?0.057). In comparative study, the results of ¹⁸F-FPYBF-2 PET/CT were comparable with those of ¹¹C-PiB, and the Mean Cortical Index (¹⁸F-FPYBF-2: 1.173?±?0.215; ¹¹C-PiB: 1.435?±?0.474) showed direct proportional relationship with each other (p?<?0.0001).

Conclusions

Our first clinical study suggest that ¹⁸F-FPYBF-2 is a useful PET tracer for the evaluation of β-amyloid deposition and that quantitative analysis of Mean Cortical Index of SUVR is a reliable diagnostic tool for the diagnosis of AD.

     

Diagnosis of recurrent prostate cancer with PET/CT imaging using the gastrin-releasing peptide receptor antagonist <Superscript>68</Superscript>Ga-RM2: Preliminary results in patients with negative or inconclusive [<Superscript>18</Superscript>F]Fluoroethylcholine-PET/CT

Purpose/background

[¹⁸F]fluoroethylcholine (¹⁸FECH) has been shown to be a valuable PET-tracer in recurrent prostate cancer (PCa), but still has limited accuracy. RM2 is a gastrin-releasing peptide receptor (GRPr) antagonist that binds to GRPr on PCa cells. Recent studies suggest that GRPr imaging with PET/CT is a promising technique for staging and restaging of PCa. We explore the value of GRPr-PET using the ⁶⁸Ga-labeled GRPr antagonist RM2 in a selected population of patients with biochemically recurrent PCa and a negative/inconclusive ¹⁸FECH-PET/CT.

Material and methods

In this retrospective study 16 men with biochemical PCa relapse and negative (n = 14) or inconclusive (n = 2) ¹⁸FECH-PET/CT underwent whole-body ⁶⁸Ga-RM2-PET/CT. Mean time from ¹⁸FECH-PET/CT to ⁶⁸Ga-RM2-PET/CT was 6.1 ± 6.8 months. Primary therapies in these patients were radical prostatectomy (n = 13; 81.3%) or radiotherapy (n = 3; 18.7%). 14/16 patients (87.5%) had already undergone salvage therapies because of biochemical relapse prior to ⁶⁸Ga-RM2-PET/CT imaging. Mean ± SD PSA at ⁶⁸Ga-RM2-PET/CT was 19.4 ± 53.5 ng/ml (range 1.06–226.4 ng/ml).

Results

⁶⁸Ga-RM2-PET/CT showed at least one region with focal pathological uptake in 10/16 patients (62.5%), being suggestive of local relapse (n = 4), lymph node metastases (LNM; n = 4), bone metastases (n = 1) and lung metastasis with hilar LNM (n = 1). Seven of ten positive ⁶⁸Ga-RM2 scans were positively confirmed by surgical resection and histology of the lesions (n = 2), by response to site-directed therapies (n = 2) or by further imaging (n = 3). Patients with a positive ⁶⁸Ga-RM2-scan showed a significantly higher median PSA (6.8 ng/ml, IQR 10.2 ng/ml) value than those with a negative scan (1.5 ng/ml, IQR 3.1 ng/ml; p = 0.016). Gleason scores or concomitant antihormonal therapy had no apparent impact on the detection of recurrent disease.

Conclusion

Even in this highly selected population of patients with known biochemical recurrence but negative or inconclusive ¹⁸FECH-PET/CT, a ⁶⁸Ga-RM2-PET/CT was helpful to localize PCa recurrence in the majority of the cases. Thus, ⁶⁸Ga-RM2-PET/CT deserves further investigation as a promising imaging modality for imaging PCa recurrence.

     

PET/CT comparing <Superscript>68</Superscript>Ga-DOTATATE and other radiopharmaceuticals and in comparison with CT/MRI for the localization of sporadic metastatic pheochromocytoma and paraganglioma

Purpose

Pheochromocytomas/paragangliomas (PPGLs) and their metastases are tumors that predominantly express somatostatin receptor 2 (SSR2). ⁶⁸Ga-DOTA(0)-Tyr(3)-octreotate (⁶⁸Ga-DOTATATE) is a PET radiopharmaceutical with both high and selective affinity for SSRs. The purpose of this study was to evaluate the utility of ⁶⁸Ga-DOTATATE in comparison with other specific and nonspecific radiopharmaceuticals recommended in the current guidelines for the localization of metastatic sporadic PPGL by PET/CT.

Methods

This prospective study included 22 patients (15 men, 7 women; aged 50.0?±?13.9 years) with confirmed metastatic PPGL, a negative family history for PPGL, and negative genetic testing, who underwent ⁶⁸Ga-DOTATATE, ¹⁸F-fluoro-2-deoxy-D-glucose (¹⁸F-FDG) PET/CT, and CT/MRI. Only 12 patients underwent an additional ¹⁸F-fluorodihydroxyphenylalanine (¹⁸F-FDOPA) PET/CT scan and only 11 patients underwent an additional ¹⁸F-fluorodopamine (¹⁸F-FDA) PET/CT scan. The rates of detection of metastatic lesions were compared among all the imaging studies. A composite of all functional and anatomical imaging studies served as the imaging comparator.

Results

⁶⁸Ga-DOTATATE PET/CT showed a lesion-based detection rate of 97.6 % (95 % confidence interval, CI, 95.8 – 98.7 %). ¹⁸F-FDG PET/CT, ¹⁸F-FDOPA PET/CT, ¹⁸F-FDA PET/CT, and CT/MRI showed detection rates of 49.2 % (CI 44.5 – 53.6 %; p?<?0.01), 74.8 % (CI 69.0 – 79.9 %); p?<?0.01), 77.7 % (CI 71.5 – 82.8 %; p?<?0.01), and 81.6 % (CI 77.8 – 84.8 %; p?<?0.01), respectively.

Conclusion

The results of this study demonstrate the superiority of ⁶⁸Ga-DOTATATE PET/CT in the localization of sporadic metastatic PPGLs compared to all other functional and anatomical imaging modalities, and suggest modification of future guidelines towards this new imaging modality.

     

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.