<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.

     

<Superscript>18</Superscript>F-FDG PET/MRI evaluation of retroperitoneal fibrosis: a simultaneous multiparametric approach for diagnosing active disease

Purpose

The aim of this study was to evaluate integrated ¹⁸F-FDG PET/MRI as a one-stop diagnostic procedure in the assessment of (active) idiopathic retroperitoneal fibrosis (RPF)

Methods

A total of 22 examinations comprising a PET/CT scan followed by a PET/MRI scan in 17 patients (13 men, 4 women, age 58?±?11 years) with histopathologically confirmed RPF at diagnosis or during follow-up under steroid therapy were analysed in correlation with laboratory inflammation markers (ESR, CRP). The patient cohort was subdivided into two groups: 6 examinations in untreated and 16 in treated patients. Tissue formations in typically periaortic localization suggestive of RPF were visually and quantitatively evaluated. The PET analysis included the assessment of SUVmax and a qualitative score for FDG uptake in RPF tissue in relation to the uptake in the liver. MRI analysis included evaluation of the T2-weighted image signal intensity, contrast enhancement and diffusion restriction (ADC values). Mean values were compared using the Mann-Whitney U test. ADC, SUVmax and ESR values were correlated using Pearson’s correlation.

Results

MRI analysis revealed restricted diffusion in 100 % and 56 %, hyperintense T2 signal in 100 % and 31 %, and contrast enhancement in the periaortic tissue formation suggestive of RPF in 100 % and 62.5 % in the untreated and treated patients, respectively. In the qualitative and quantitative PET analysis, statistically significant differences were found for mean FDG uptake scores (2.5?±?0.8 in untreated patients and 1.1?±?0.9 in treated patients) and mean SUVmax (7.8?±?3.5 and 4.1?±?2.2, respectively). A strong correlation was found between the ADC values and SUVmax (Pearson r? ??0.65, P?=?0.0019), and between ESR and CRP values and SUVmax (both r?=?0.45, P?=?0.061).

Conclusion

Integrated ¹⁸F-FDG PET/MRI shows high diagnostic potential as a one-stop diagnostic procedure for the assessment of (active) RPF providing multiparametric supportive information.

     

Diagnostic Value of <Superscript>18</Superscript>F-FDG PET/CT and MRI in the Preoperative Evaluation of Uterine Carcinosarcoma

Purpose

This study aimed to compare the diagnostic value of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) and magnetic resonance imaging (MRI) in the preoperative evaluation of uterine carcinosarcoma.

Methods

Fifty-four women with pathologically confirmed uterine carcinosarcoma who underwent preoperative FDG PET/CT and MRI from June 2006 to November 2016 were included. Pathologic findings from primary tumor lesions, para-aortic and pelvic lymph node (LN) areas, and peritoneal seeding lesions were compared with the FDG PET/CT and MRI findings. The maximum standardized uptake value (SUVmax) of the primary tumor and LN was obtained. The tumor-to-liver ratio (TLR) was calculated by dividing the SUVmax of the primary tumor or LN by the mean SUV of the liver.

Results

For detecting primary tumor lesions (n?=?54), the sensitivity and accuracy of FDG PET/CT (53/54) and MRI (53/54) were 98.2%. The sensitivity, specificity, and accuracy of FDG PET/CT versus MRI were as follows: 63.2% (12/19) versus 26.3% (5/19), 100% (35/35) versus 100% (35/35), and 87.0% versus 74.0%, respectively, for pelvic LN areas (p?=?0.016); 85.7% (12/14) versus 42.9% (6/14), 90% (36/40) versus 97.5% (39/40), and 88.9% versus 83.3%, respectively, for para-aortic LN areas (p?=?0.004); and 59.4% (19/32) versus 50% (16/32), 100% (22/22) versus 100% (22/22), and 75.9% versus 70.4%, respectively, for peritoneal seeding lesions (p?=?0.250). For distant metastasis, the sensitivity, specificity, and accuracy of FDG PET/CT were 100 (8/8), 97.8 (45/46), and 98.2%, respectively.

Conclusions

FDG PET/CT showed superior diagnostic accuracy compared to MRI in detecting pelvic and para-aortic LN metastasis in patients with uterine carcinosarcoma. Moreover, FDG PET/CT facilitated the identification of distant metastasis.

     

Multimodal correlation of dynamic [<Superscript>18</Superscript>F]-AV-1451 perfusion PET and neuronal hypometabolism in [<Superscript>18</Superscript>F]-FDG PET

Purpose

Cerebral glucose metabolism measured with [18F]-FDG PET is a well established marker of neuronal dysfunction in neurodegeneration. The tau-protein tracer [18F]-AV-1451 PET is currently under evaluation and shows promising results. Here, we assess the feasibility of early perfusion imaging with AV-1451 as a substite for FDG PET in assessing neuronal injury.

Methods

Twenty patients with suspected neurodegeneration underwent FDG and early phase AV-1451 PET imaging. Ten one-minute timeframes were acquired after application of 200 MBq AV-1451. FDG images were acquired on a different date according to clinical protocol. Early AV-1451 timeframes were coregistered to individual FDG-scans and spatially normalized. Voxel-wise intermodal correlations were calculated on within-subject level for every possible time window. The window with highest pooled correlation was considered optimal. Z-transformed deviation maps (ZMs) were created from both FDG and early AV-1451 images, comparing against FDG images of healthy controls.

Results

Regional patterns and extent of perfusion deficits were highly comparable to metabolic deficits. Best results were observed in a time window from 60 to 360 s (r = 0.86). Correlation strength ranged from r = 0.96 (subcortical gray matter) to 0.83 (frontal lobe) in regional analysis. ZMs of early AV-1451 and FDG images were highly similar.

Conclusion

Perfusion imaging with AV-1451 is a valid biomarker for assessment of neuronal dysfunction in neurodegenerative diseases. Radiation exposure and complexity of the diagnostic workup could be reduced significantly by routine acquisition of early AV-1451 images, sparing additional FDG PET.

     

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

Purpose

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

Methods

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

Results

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

Conclusions

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

     

<Superscript>18</Superscript>F-FDG PET/CT for the Diagnosis of Malignant and Infectious Complications After Solid Organ Transplantation

Purpose

Infection and malignancy represent two common complications after solid organ transplantation, which are often characterized by poorly specific clinical symptomatology. Herein, we have evaluated the role of ¹⁸F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) in this clinical setting.

Methods

Fifty-eight consecutive patients who underwent FDG PET/CT after kidney, lung or heart transplantation were included in this retrospective analysis. Twelve patients underwent FDG PET/CT to strengthen or confirm a diagnostic suspicion of malignancies. The remaining 46 patients presented with unexplained inflammatory syndrome, fever of unknown origin (FUO), CMV or EBV seroconversion during post-transplant follow-up without conclusive conventional imaging. FDG PET/CT results were compared to histology or to the finding obtained during a clinical/imaging follow-up period of at least 6 months after PET/CT study.

Results

Positive FDG PET/CT results were obtained in 18 (31 %) patients. In the remaining 40 (69 %) cases, FDG PET/CT was negative, showing exclusively a physiological radiotracer distribution. On the basis of a patient-based analysis, FDG PET/CT’s sensitivity, specificity, PPV and NPV were respectively 78 %, 90 %, 78 % and 90 %, with a global accuracy of 86 %. FDG PET/CT was true positive in 14 patients with bacterial pneumonias (n?=?4), pulmonary fungal infection (n?=?1), histoplasmosis (n?=?1), cutaneous abscess (n?=?1), inflammatory disorder (sacroiliitis) (n?=?1), lymphoma (n?=?3) and NSCLC (n?=?3). On the other hand, FDG PET/CT failed to detect lung bronchoalveolar adenocarcinoma, septicemia, endocarditis and graft-versus-host disease (GVHD), respectively, in four patients. FDG PET/CT contributed to adjusting the patient therapeutic strategy in 40 % of cases.

Conclusions

FDG PET/CT emerges as a valuable technique to manage complications in the post-transplantation period. FDG PET/CT should be considered in patients with severe unexplained inflammatory syndrome or FUO and inconclusive conventional imaging or to discriminate active from silent lesions previously detected by conventional imaging particularly when malignancy is suspected.

     

The diagnostic value of [<Superscript>18</Superscript>F]FDG PET for the detection of chronic osteomyelitis and implant-associated infection

Purpose

The diagnosis of osteomyelitis and implant-associated infections in patients with nonspecific laboratory or radiological findings is often unsatisfactory. We retrospectively evaluated the contributions of [¹⁸F]FDG PET and [¹⁸F]FDG PET/CT to the diagnosis of osteomyelitis and implant-associated infections, enabling timely and appropriate decision-making for further therapy options.

Methods

[¹⁸F]FDG PET or PET/CT was performed in 215 patients with suspected osteomyelitis or implant-associated infections between 2000 and 2013. We assessed the diagnostic accuracy of both modalities together and separately with reference to intraoperative microbial findings, with a mean clinical follow-up of 69?±?49 months.

Results

Infections were diagnosed clinically in 101 of the 215 patients. PET and PET/CT scans revealed 87 true-positive, 76 true-negative, 38 false-positive, and 14 false-negative results, indicating a sensitivity of 86 %, a specificity of 67 %, a positive predictive value (PPV) of 70 %, a negative predictive value (NPV) of 84 % and an accuracy of 76 %. The sensitivity of PET/CT was 88 %, but specificity, PPV, NPV and accuracy (76 %, 76 %, 89 % and 82 %, respectively) were higher than those of stand-alone PET.

Conclusion

[¹⁸F]FDG PET is able to identify with high sensitivity the presence of osteomyelitis in orthopaedic surgery patients with nonspecific clinical symptoms of infection.

     

Diagnostic and prognostic value of <Superscript>18</Superscript>F-FDG PET/CT for axillary lymph node staging in patients with breast cancer

Purpose

To investigate the diagnostic and prognostic value of ¹⁸F-FDG-PET/CT for axillary lymph node (LN) staging in breast cancer patients, employing histologic evaluation as the reference.

Methods

Among 196 patients with biopsy-proven breast cancer who had undergone ¹⁸F-FDG-PET/CT before mastectomy or breast-conserving surgery with sentinel LN biopsy and/or axillary LN dissection, 200 axillae were retrospectively analyzed by visual assessment and quantitatively using SUVmax. LN SUVmax as well as other clinicopathological features were assessed for their prognostic value using the log-rank test and Cox method.

Results

Metastasis was diagnosed histopathologically in 56 (28 %) axillae. The sensitivity, specificity, and accuracy of visual PET/CT for diagnosing node metastasis were 55.4, 95.8, and 84.5 %, respectively. When the optimal discriminative SUVmax cutoff was 1.5, these figures were 51.8, 97.2, and 84.5 %, respectively. Fourteen of 55 patients (25.5 %) with LN metastases suffered a recurrence during follow-up (median 39 months). Patients with a high nodal SUVmax (≥1.7) had a significantly lower progression-free survival rate than those with a low SUVmax (p = 0.0499). Axillary nodal and primary tumor SUVmax as well as estrogen receptor status were significantly associated with recurrence.

Conclusion

Axillary nodal SUVmax may be a prognostic indicator of disease recurrence in patients with axillary LN metastases.

     

Value of <Superscript>18</Superscript>F-FDG PET/CT for therapeutic assessment of patients with polymyalgia rheumatica receiving tocilizumab as first-line treatment

Purpose

To evaluate the use of ¹⁸F-FDG PET/CT for the assessment of tocilizumab (TCZ) as first-line treatment in patients with polymyalgia rheumatica (PMR).

Methods

Patients with PMR were prospectively enrolled in a multicentre clinical trial assessing TCZ therapy (the TENOR trial). The patients underwent FDG PET/CT at baseline, after the first infusion of TCZ (TCZ 1) and after the last infusion of TCZ (TCZ 3). Responses to treatment were evaluated in terms of the PMR activity score (PMR-AS), and the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) laboratory tests. Maximal standardized uptake value (SUVmax) was used for assessment of FDG uptake in regions usually affected in PMR (spinous processes, hips, shoulders, sternoclavicular region and ischial tuberosities). The Wilcoxon test was applied to evaluate the changes in parameters after the infusions and Spearman’s rank correlation test was applied to assess the correlations between SUVmax and PMR-AS, CRP and ESR.

Results

Of 21 patients included in the trial, 18 were evaluated. The median bioclinical parameter values decreased after TCZ 1 (PMR-AS from 38.2 to 15.7, CRP from 65.2 to 0.4 mg/l and ESR from 49 to 6.5 mm; all p?<?0.05) as did the median SUVmax (from 5.8 to 5.2; p?<?0.05). All values also decreased after TCZ 3 (PMR-AS from 38.2 to 3.9, CRP from 65.2 to 0.2, ESR from 49 to 2, and SUVmax from 5.8 to 4.7; p?<?0.05). In a region-based analysis, all SUVmax were significantly reduced after TCZ 3, except the values for the cervical spinous processes and shoulder regions. With regard to correlations, few significant differences were found between ?SUVmax and the other parameters including ?PMR-AS, ?CRP and ?ESR in the patient-based and region-based analysis.

Conclusion

FDG uptake decreased significantly but moderately after TCZ therapy in PMR patients, and might reflect disease activity.

     

Visual and statistical analysis of <Superscript>18</Superscript>F-FDG PET in primary progressive aphasia

Purpose

Diagnosing progressive primary aphasia (PPA) and its variants is of great clinical importance, and fluorodeoxyglucose (FDG) positron emission tomography (PET) may be a useful diagnostic technique. The purpose of this study was to evaluate interobserver variability in the interpretation of FDG PET images in PPA as well as the diagnostic sensitivity and specificity of the technique. We also aimed to compare visual and statistical analyses of these images.

Methods

There were 10 raters who analysed 44 FDG PET scans from 33 PPA patients and 11 controls. Five raters analysed the images visually, while the other five used maps created using Statistical Parametric Mapping software. Two spatial normalization procedures were performed: global mean normalization and cerebellar normalization. Clinical diagnosis was considered the gold standard.

Results

Inter-rater concordance was moderate for visual analysis (Fleiss’ kappa 0.568) and substantial for statistical analysis (kappa 0.756–0.881). Agreement was good for all three variants of PPA except for the nonfluent/agrammatic variant studied with visual analysis. The sensitivity and specificity of each rater’s diagnosis of PPA was high, averaging 87.8 and 89.9 % for visual analysis and 96.9 and 90.9 % for statistical analysis using global mean normalization, respectively. In cerebellar normalization, sensitivity was 88.9 % and specificity 100 %.

Conclusion

FDG PET demonstrated high diagnostic accuracy for the diagnosis of PPA and its variants. Inter-rater concordance was higher for statistical analysis, especially for the nonfluent/agrammatic variant. These data support the use of FDG PET to evaluate patients with PPA and show that statistical analysis methods are particularly useful for identifying the nonfluent/agrammatic variant of PPA.

     

Long-term follow-up and role of FDG PET in advanced pancreatic neuroendocrine patients treated with <Superscript>177</Superscript>Lu-D OTATATE

Purpose

Lu-DOTATATE (Lu-PRRT) is a valid therapeutic option in differentiated pancreatic neuroendocrine tumors (P-NETs). FDG PET seems to be an important prognostic factor in P-NETs. We evaluated the efficacy of Lu-PRRT and the role of FDG PET in 60 patients with advanced P-NETs.

Methods

From March 2008 to June 2011, 60 consecutive patients with P-NETs were enrolled in the study. Follow-up lasted until March 2016. Eligible patients were treated with two different total cumulative activities (18.5 or 27.8 GBq in 5 cycles every 6–8 weeks), according to kidney and bone marrow parameters.

Results

Twenty-eight patients received a mean full activity (FA) of 25.9 GBq and 32 a mean reduced activity (RA) of 18.5 GBq. The disease control rate (DCR), defined as the sum of CR+PR+SD was 85.7 % in the FA group and 78.1 % in the RA group. Median progression-free survival (mPFS) was 53.4 months in the FA group and 21.7 months in the RA group (P?=?0.353). Median overall survival (mOS) was not reached (nr) in FA patients and was 63.8 months in the RA group (P?=?0.007). Fifty-five patients underwent an FDG PET scan before Lu-PRRT, 32 (58 %) showing an increased FDG uptake in tumor sites. mPFS was 21.1 months in FDG PET-positive patients and 68.7 months in the FDG PET-negative group (P?<?0.0002), regardless of the total activity administered.

Conclusion

Both FA and RA are active in patients undergoing Lu-PRRT. However, an FA of 27.8 GBq of Lu-PRRT prolongs PFS and OS compared to an RA of 18.5 GBq. Our results indicate that FDG PET is an independent prognostic factor in this patient setting.

     

Optimization of scan initiation timing after <Superscript>11</Superscript>C-methionine administration for the diagnosis of suspected recurrent brain tumors

Objective

¹¹C-Methionine (MET) positron emission tomography (PET) imaging is a valuable technique for the evaluation of primary and recurrent brain tumors. Many studies have used MET-PET for data acquisition starting at 20 min after the tracer injection, while others have used scan initiation times at 5–15 min postinjection. No previous studies have identified the best acquisition timing during MET-PET imaging for suspected recurrent brain tumors. Here we sought to determine the optimal scan initiating timing after MET administration for the detection of recurrent brain tumors.

Materials and methods

Twenty-three consecutive patients with suspected recurrent brain tumors underwent MET-PET examinations. Brain PET images were reconstructed from the four serial data sets (10–15, 15–20, 20–25, and 25–30 min postinjection) that were obtained using the list-mode acquisition technique. We determined the maximal standardized uptake values (SUVmax) of the target lesions and the target-to-normal-tissue ratios (TNRs), calculated as the SUVmax to the SUVmean of a region of interest placed on the normal contralateral frontal cortex. Target lesions without significant MET uptake were excluded.

Results

Thirty-one lesions from 23 patients were enrolled. There were no significant differences in MET SUVmax or TNR values among the PET images that were reconstructed with the data extracted from the four phases postinjection.

Conclusion

The MET uptake in the suspected recurrent brain tumors was comparable among all data extraction time phases from 10 to 30 min postinjection. The scan initiation time of MET-PET at 10 min after the injection is allowable for the detection of recurrent brain tumors. The registration identification number of the original study is 1002.

     

Reproducibility of standardized uptake values of same-day randomized <Superscript>68</Superscript>Ga-PSMA-11 PET/CT and PET/MR scans in recurrent prostate cancer patients

Objective

Positron emission tomography in association with magnetic resonance imaging (PET/MR) and ⁶⁸Ga-PSMA-11 has shown superior detection in recurrent prostate cancer patients as compared to PET/computed tomography (PET/CT). There are, however, several technological differences between PET/CT and PET/MR systems which affect the PET image quality. The objective of this study was to assess the reproducibility of PET/CT and PET/MR SUV’s in recurrent prostate cancer patients. We randomized the patients regarding the order of the PET/CT and PET/MR scans to reduce the influence of tracer uptake as a function of time.

Methods

Thirty patients, all with biochemical recurrence after radical prostatectomy, underwent whole-body PET/CT and PET/MR scans after intravenous injection of a single dose of ⁶⁸Ga-PSMA-11. Fifteen patients underwent PET/CT first and 15 patients underwent PET/MR first. Volumes of interest on tumor lesions were outlined and maximum standardized uptake value (SUVmax) corrected for lean body mass was calculated. Correlation and agreement between scans were assessed by generalized linear mixed-effects models and Bland–Altman analysis. The association between SUV, patient characteristics and imaging parameters was assessed.

Results

Eighteen of the 30 evaluated patients had at least one positive lesion, giving an overall detection rate of 60%. In total, there were 34 visible lesions: 5 local recurrences, 22 lymph node metastases and 7 bone metastases. One group acquired PET/CT and PET/MR at median time points of 63.0 and 159.0 min, while the other group acquired PET/MR and PET/CT at median time points of 92.0 and 149.0 min. SUVmax between scans was linearly correlated, described by the equation Y(PET/CT SUVmax)?=?0.75?+?1.00?×?(PET/MR SUVmax), on average 20% higher on PET/CT than on PET/MR. SUV associated significantly only with type of lesion, scan time post-injection and acquisition time per bed position.

Conclusions

SUVmax from PET/CT and PET/MR are linearly correlated, on average 20% higher on PET/CT than on PET/MR and should, therefore, not be used interchangeably in patient follow-up.

     

Repeatability of tumour hypoxia imaging using [<Superscript>18</Superscript>F]EF5 PET/CT in head and neck cancer

Purpose

Hypoxia contributes to radiotherapy resistance and more aggressive behaviour of several types of cancer. This study was designed to evaluate the repeatability of intratumour uptake of the hypoxia tracer [¹⁸F]EF5 in paired PET/CT scans.

Methods

Ten patients with newly diagnosed head and neck cancer (HNC) received three static PET/CT scans before chemoradiotherapy: two with [¹⁸F]EF5 a median of 7 days apart and one with [¹⁸F]FDG. Metabolically active primary tumour volumes were defined in [¹⁸F]FDG images and transferred to co-registered [¹⁸F]EF5 images for repeatability analysis. A tumour-to-muscle uptake ratio (TMR) of 1.5 at 3 h from injection of [¹⁸F]EF5 was used as a threshold representing hypoxic tissue.

Results

In 10 paired [¹⁸F]EF5 PET/CT image sets, SUVmean, SUVmax, and TMR showed a good correlation with the intraclass correlation coefficients of 0.81, 0.85, and 0.87, respectively. The relative coefficients of repeatability for these parameters were 15%, 17%, and 10%, respectively. Fractional hypoxic volumes of the tumours in the repeated scans had a high correlation using the Spearman rank correlation test (r = 0.94). In a voxel-by-voxel TMR analysis between the repeated scans, the mean of Pearson correlation coefficients of individual patients was 0.65. The mean (± SD) difference of TMR in the pooled data set was 0.03 ± 0.20.

Conclusion

Pretreatment [¹⁸F]EF5 PET/CT within one week shows high repeatability and is feasible for the guiding of hypoxia-targeted treatment interventions in HNC.

     

Effect of <Superscript>18</Superscript>F-fluorodeoxyglucose extravasation on time taken for tumoral uptake to reach a plateau: animal and clinical PET analyses

Objective

The present study aimed to investigate the effect of ¹⁸F-fluorodeoxyglucose (FDG) extravasation on the time taken for tumoral uptake to reach a plateau.

Methods

For the animal experiment, FDG extravasation was conducted in the tails of HCT116 tumor-bearing xenograft mice models in three groups (no extravasation, 40 % extravasation, and 80 % extravasation; n = 5, each). Dynamic positron emission tomography (PET) images were acquired over a period of 2 h following injection. Time–activity curves for FDG in the tails and tumors were calculated. For the clinical experiment, 22 patients (male:female, 14:8; age range, 70.8 ± 9.2 years) were subjected to PET/computed tomography (PET/CT) 1 h after the injection of FDG. The inclusion criteria were as follows: (1) submitted to both whole-body and subsequent regional scanning; (2) entire extravasation activity visualized in the whole-body images; (3) tumor visualized on both whole-body and additional regional images; and (4) status of tumor either confirmed by biopsy or clinically suspected for malignancy. The standardized uptake values (SUVs) of the tumors (on the whole-body and additional PET images) and extravasation sites were recorded.

Results

There were no significant differences in the time taken for tumoral uptake to reach a plateau and that to reach minimum activity at the extravasation site among the three groups of mice. However, the mean tumoral activity and activity at the extravasation site were negatively correlated at 1 h post-injection. According to the clinical PET findings, the differences in SUV between the whole-body and regional images were not significantly correlated with the interval between injection of FDG and start of whole-body scanning, interval between the start of whole-body scanning and start of regional scanning, extravasation volume, maximum SUV of the extravasation site, or total activity at the extravasation site.

Conclusions

The time taken for tumoral uptake to reach a plateau is not affected by extravasation, even at extensive degrees. Thus, in routine practice, the imaging time of approximately 60 min post-injection need not be modified even if extravasation is identified. However, tumor SUV may be underestimated in cases of extravasation.

     

Biphasic <Superscript>68</Superscript>Ga-PSMA-HBED-CC-PET/CT in patients with recurrent and high-risk prostate carcinoma

Purpose

Binding of ⁶⁸Ga-PSMA-HBED-CC (⁶⁸Ga-PSMA) at prostate cancer (PC) cells increases over time. A biphasic protocol may help separating benign from tumor lesions. The aim of this study was the retrospective evaluation of a diagnostic incremental value of a dual-time point (biphasic) ⁶⁸Ga-PSMA-PET/CT in patients with prostate cancer.

Methods

Retrospective analysis of 35 consecutive patients (49–78 years, median 71) with newly diagnosed PC (12/35) or recurrence of PC (23/35). PET/CT (Gemini TF16, Philips) was acquired 1 h and 3 h p. i. of 140–392 MBq (300 MBq median) ⁶⁸Ga-PSMA, followed by a diagnostic contrast CT. PET findings were correlated with histology or unequivocal CT findings. Semiquantitative PET data (SUVmax, SUV mean) were acquired and target-to-background-ratios (T/B-ratio) were calculated for benign and malign lesions for both time points. Size of lymph nodes (LN) on diagnostic CT was recorded. Statistical analysis was performed for assessment of significant changes of semiquantitative PET-parameters over time and for correlation of size and uptake of lymph nodes.

Results

One hundred and four lesions were evaluated. Sixty lesions were referenced by histology or unequivocal CT findings, including eight (13.3 %) histopathologically benign lymph nodes, 12 (20 %) histopathologically lymph node metastases, 12 (20 %) primary tumors, three (5 %) local recurrences, and 25 (41.7 %) bone metastases. Forty-four lesions were axillary LN with normal CT-appearance. Benign lesions had significantly lower SUVmax and T/B-ratios compared with malignant findings. Malign lesions showed a significant increase of both parameters over time compared to benign findings. There was no correlation between LN size and SUVmax. The sensitivity, specificity, the positive predictive value and negative predictive value of PET/CT regarding pelvic LN was 94 %, 99 %, 89 %, and 99.5 %, respectively.

Conclusions

In contrast to benign tissues, the uptake of proven tumor lesions increases on ⁶⁸Ga-PSMA-PET/CT over time. A biphasic PET-study may lead to a better detection of tumor lesions in unequivocal findings.

     

Contribution of <Superscript>18</Superscript>F-FDG PET in the diagnostic assessment of fever of unknown origin (FUO): a stratification-based meta-analysis

Purpose

The aim of this study was to quantify the contribution of FDG PET to the diagnostic assessment of fever of unknown origin (FUO), taking into account the diagnostic limitations resulting from the composite nature of this entity.

Methods

The PubMed/MEDLINE database was searched from 2000 to September 2015. Original articles fulfilling the following criteria were included: (1) FUO as the initial diagnosis, (2) no immunosuppressed or nosocomial condition, (3) final diagnosis not based on PET, (4) a follow-up period specified, (5) adult population, and (6) availability of adapted data for calculation of odds ratios (ORs). ORs were computed for each study and then pooled using a random effects model. Stratification-based sensitivity analyses were finally performed using the following prespecified criteria: (a) study design, (b) PET device, (c) geographic area, and (d) follow-up period.

Results

A meta-analysis of the 14 included studies showed that normal PET findings led to an increase in the absolute final diagnostic rate of 36 % abnormal PET findings to an increase of 83 %, corresponding to a pooled OR of 8.94 (95 % CI 4.18?–?19.12, Z?=?5.65; p?<?0.00001). The design of the studies influenced the results (OR 2.92, 95 % CI 1.00?–?8.53 for prospective studies; OR 18,57, 95 % CI 7.57?–?45.59 for retrospective studies; p?=?0.01), whereas devices (dedicated or hybrid), geographic area and follow-up period did not.

Conclusion

Abnormal PET findings are associated with a substantially increased final diagnostic rate in FUO. Consequently, FDG PET could be considered for inclusion in the first-line diagnostic work-up of FUO. Further randomized prospective studies with standardized FDG PET procedures are warranted to confirm this first-line position.

     

Assessment of the diagnostic accuracy of <Superscript>18</Superscript>F-FDG PET/CT in prosthetic infective endocarditis and cardiac implantable electronic device infection: comparison of different interpretation criteria

Purpose

The diagnosis of prosthetic valve (PV) infective endocarditis (IE) and infection of cardiac implantable electronic devices (CIEDs) remains challenging. The aim of this study was to assess the usefulness of ¹⁸F-FDG PET/CT in these patients and analyse the interpretation criteria.

Methods

We included 41 patients suspected of having IE by the Duke criteria who underwent ¹⁸F-FDG PET/CT. The criteria applied for classifying the findings as positive/negative for IE were: (a) visual analysis of only PET images with attenuation-correction (AC PET images); (b) visual analysis of both AC PET images and PET images without AC (NAC PET images); (c) qualitative analysis of NAC PET images; and (d) semiquantitative analysis of AC PET images. ¹⁸F-FDG PET/CT was considered positive for IE independently of the intensity and distribution of FDG uptake. The gold standard was the Duke pathological criteria (if tissue was available) or the decision of an endocarditis expert team after a minimum 4 months follow-up.

Results

We studied 62 areas with suspicion of IE, 28 areas (45 %) showing definite IE and 34 (55 %) showing possible IE. Visual analysis of only AC PET images showed poor diagnostic accuracy (sensitivity 20 %, specificity 57 %). Visual analysis of both AC PET and NAC PET images showed excellent sensitivity (100 %) and intermediate specificity (73 %), focal uptake being more frequently associated with IE. The accuracy of qualitative analysis of NAC PET images depended on the threshold: the maximum sensitivity, specificity and accuracy achieved were 88 %, 80 %, 84 %, respectively. In the semiquantitative analysis of AC PET images, SUVmax was higher in areas of confirmed IE than in those without IE (?SUVmax 2.2, p?<?0.001). When FDG uptake was twice that in the liver, IE was always confirmed, and SUVmax 5.5 was the optimal threshold for IE diagnosis using ROC curve analysis (area under the curve 0.71).

Conclusion

The value of ¹⁸F-FDG PET/CT in the diagnosis of suspected IE of PVs and CIEDs is highly dependent on patient preparation and the method used for image interpretation. Based on our results, the best method is to consider a study positive for IE when FDG uptake is present in both AC PET and NAC PET images.

     

<Superscript>18</Superscript>F-FDG PET/CT can predict chemosensitivity and proliferation of epithelial ovarian cancer via SUVmax value

Purpose

This study aimed to explore the clinical and prognostic significance of ¹⁸F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) in epithelial ovarian cancer (EOC).

Methods

We retrospectively investigated 48 EOC patients who underwent preoperative ¹⁸F-FDG PET/CT and primary cytoreductive surgery at our hospital between January 2010 and June 2015. None of these patients received neoadjuvant chemotherapy. PET/CT parameters including the maximum and average standardized uptake value (SUVmax, SUVavg), the metabolic tumor volume (MTV) were measured. Tumor proliferation marker Ki67 was evaluated using immunohistochemistry. The relationships between the PET/CT parameters and chemosensitivity, tumor proliferation, and overall survival (OS) were analyzed, respectively.

Results

The median (range) SUVmax, SUVavg, and MTV values were 11.42 (3.14–20.20), 4.8 (2.55–9.47), and 150.11 (0.19–792.46), respectively. Overall, 93.8% (45/48) of patients had high-grade serous ovarian cancer. The SUVmax value had a positive correlation with the Ki67 index (P?=?0.030, r?=?0.314), and a higher SUVmax level was associated with chemosensitivity (P?=?0.026). However, neither SUVavg nor MTV had associations with the patients’ clinicopathological parameters. None of these three PET/CT parameters were found to be potential predictors of OS.

Conclusions

Preoperative ¹⁸F-FDG PET/CT had a predictive value on chemosensitivity and proliferation after primary debulking surgery in EOC patients noninvasively.

     

<Superscript>68</Superscript>Ga-PSMA-11 PET/CT in primary staging of prostate carcinoma: preliminary results on differences between black and white South-Africans

Purpose

The incidence of prostate cancer is 60% higher and the mortality rate is two- to three-times greater in black versus white men. We report on differences in ⁶⁸Ga-PSMA-11 PET/CT imaging findings in 77 black South-African (BSAs) and 18 white South-African (WSAs) treatment-naïve primary prostate carcinoma (PPC) patients.

Methods

⁶⁸Ga-PSMA-11 PET/CT imaging findings were compared to histological, biochemical and morphological imaging data. Patients were grouped into three Gleason grade groups (GG), GG 1 (scores 3 + 3 and 3 + 4), GG2 (scores 4 + 3 and 4 + 4) and GG3 (scores 9 and 10), and the PSA difference among the groups was determined. Inter-racial difference in SUVmax of the primary tumor as well as its correlation with serum PSA were also determined.

Results

Ninety-three out of 95 PPC where readily identified on ⁶⁸Ga-PSMA-11 PET/CT imaging. Median PPC SUVmax and serum PSA values proved significantly higher (p = 0.033 and p = 0.003) in GG3 patients (median 16.4 and 180 ng/ml) when compared to GG1 patients (median 9.6 and 25.1 ng/ml) or GG2 patients (median 8.8 and 46.2 ng/ml). SUVmax significantly correlated with serum PSA-values (r = 0.377 (p = 0.0001)). Age, frequency of lymph node involvement and distant metastases, and GGs (p ≥ 0.153) were similar in BSAs and WSAs, both median serum PSA-values as well as SUVmax values proved significantly higher in BSAs when compared to WSAs, respectively, 81.6 ng/ml versus 14.5 ng/ml (p = 0.0001) and 11.9 versus 4.38 (p = 0.004). Moreover, Gleason-score normalized median SUVmax values proved 2.5 times higher in BSAs when compared to WSAs (p = 0.005).

Conclusion

SUVmax values proved significantly related to GG and to be significantly higher in BSAs when compared to WSAs. Also, SUVmax significantly correlated with serum PSA values, which was significantly higher in BSAs when compared with WSAs.