<Superscript>68</Superscript>Ga-PSMA-HBED-CC PET imaging in breast carcinoma patients

Background

To report on imaging findings using ⁶⁸Ga-PSMA-HBED-CC PET in a series of 19 breast carcinoma patients.

Methods

⁶⁸Ga-PSMA-HBED-CC PET imaging results obtained were compared to routinely performed staging examinations and analyzed as to lesion location and progesterone receptor status.

Results

Out of 81 tumor lesions identified, 84% were identified on ⁶⁸Ga-PSMA-HBED-CC PET. ⁶⁸Ga-PSMA-HBED-CC SUVmean values of distant metastases proved significantly higher (mean, 6.86, SD, 5.68) when compared to those of primary or local recurrences (mean, 2.45, SD, 2.55, p?=?0.04) or involved lymph nodes (mean, 3.18, SD, 1.79, p?=?0.011). SUVmean values of progesterone receptor-positive lesions proved not significantly different from progesterone receptor-negative lesions. SUV values derived from FDG PET/CT, available in seven patients, and ⁶⁸Ga-PSMA-HBED-CC PET/CT imaging proved weakly correlated (r?=?0.407, p?=?0.015).

Conclusions

⁶⁸Ga-PSMA-HBED-CC PET/CT imaging in breast carcinoma confirms the reported considerable variation of PSMA expression on human solid tumors using immunohistochemistry.

     

Utility of <Superscript>18</Superscript>F-fluoroestradiol (<Superscript>18</Superscript>F-FES) PET/CT imaging as a pharmacodynamic marker in patients with refractory estrogen receptor-positive solid tumors receiving Z-endoxifen therapy

Background

Z-endoxifen is the most potent of the metabolites of tamoxifen, and has the potential to be more effective than tamoxifen because it bypasses potential drug resistance mechanisms attributable to patient variability in the expression of the hepatic microsomal enzyme CYP2D6. ¹⁸F-FES is a positron emission tomography (PET) imaging agent which selectively binds to estrogen receptor alpha (ER-α) and has been used for non-invasive in vivo assessment of ER activity in tumors. This study utilizes ¹⁸F-FES PET imaging as a pharmacodynamic biomarker in patients with ER+ tumors treated with Z-endoxifen.

Methods

Fifteen patients were recruited from a parent therapeutic trial of Z-endoxifen and underwent imaging with ¹⁸F-FES PET at baseline. Eight had positive lesions on the baseline scan and underwent follow-up imaging with ¹⁸F-FES 1–5 days post administration of Z-endoxifen.

Results

Statistically significant changes (p?=?0.0078) in standard uptake value (SUV)-Max were observed between the baseline and follow-up scans as early as 1 day post drug administration.

Conclusion

F-FES PET imaging could serve as a pharmacodynamic biomarker for patients treated with ER-directed therapy.

     

Kinetic analysis of the translocator protein positron emission tomography ligand [<Superscript>18</Superscript>F]GE-180 in the human brain

Purpose

PET can image neuroinflammation by targeting the translocator protein (TSPO), which is upregulated in activated microglia. The high nonspecific binding of the first-generation TSPO radioligand [¹¹C]PK-11195 limits accurate quantification. [¹⁸F]GE-180, a novel TSPO ligand, displays superior binding to [¹¹C]PK-11195 in vitro. Our objectives were to: (1) evaluate tracer characteristics of [¹⁸F]GE-180 in the brains of healthy human subjects; and (2) investigate whether the TSPO Ala147Thr polymorphism influences outcome measures.

Methods

Ten volunteers (five high-affinity binders, HABs, and five mixed-affinity binders, MABs) underwent a dynamic PET scan with arterial sampling after injection of [¹⁸F]GE-180. Kinetic modelling of time–activity curves with one-tissue and two-tissue compartment models and Logan graphical analysis was applied to the data. The primary outcome measure was the total volume of distribution (V _T) across various regions of interest (ROIs). Secondary outcome measures were the standardized uptake values (SUV), the distribution volume and SUV ratios estimated using a pseudoreference region.

Results

The two-tissue compartment model was the best model. The average regional delivery rate constant (K ₁) was 0.01 mL cm^?3 min^?1 indicating low extraction across the blood–brain barrier (1 %). The estimated median V _T across all ROIs was also low, ranging from 0.16 mL cm^?3 in the striatum to 0.38 mL cm^?3 in the thalamus. There were no significant differences in V _T between HABs and MABs across all ROIs.

Conclusion

A reversible two-tissue compartment model fitted the data well and determined that the tracer has a low first-pass extraction (approximately 1 %) and low V _T estimates in healthy individuals. There was no observable dependency on the rs6971 polymorphism as compared to other second-generation TSPO PET tracers. Investigation of [¹⁸F]GE-180 in populations with neuroinflammatory disease is needed to determine its suitability for quantitative assessment of TSPO expression.

     

Assessment of intratumor heterogeneity in mesenchymal uterine tumor by an <Superscript>18</Superscript>F-FDG PET/CT texture analysis

Objective

The aim of this study was to retrospectively evaluate the clinical significance of ¹⁸F-FDG PET/CT textural features for discriminating uterine sarcoma from leiomyoma.

Methods

Fifty-five patients with suspected uterine sarcoma based on ultrasound and MRI findings who underwent pretreatment ¹⁸F-FDG PET/CT were included. Fifteen patients were histopathologically proven to have uterine sarcoma, 14 patients by surgical operation and one by biopsy, and 40 patients were diagnosed with leiomyoma by surgical operation or in a follow-up for at least 2 years. A texture analysis was performed on PET/CT images from which second- and higher order textural features were extracted in addition to standardized uptake values (SUVs) and other first-order features. The accuracy of PET features for differentiating between uterine sarcoma and leiomyoma was evaluated using a receiver-operating-characteristic (ROC) analysis.

Results

The intratumor distribution of ¹⁸F-FDG was more heterogeneous in uterine sarcoma than in leiomyoma. Entropy, correlation, and uniformity calculated from normalized gray-level co-occurrence matrices and SUV standard deviation derived from histogram statistics showed greater area under the ROC curves (AUCs) than did maximum SUV for differentiating between sarcoma and leiomyoma. Entropy, as a single feature, yielded the greatest AUC of 0.974 and the optimal cut-off value of 2.85 for entropy provided 93% sensitivity, 90% specificity, and 92% accuracy. When combining conventional features with textural ones, maximum SUV (cutoff: 6.0) combined with entropy (2.85) and correlation (0.73) provided the best diagnostic performance (100% sensitivity, 94% specificity, and 95% accuracy).

Conclusions

In combination with the conventional histogram statistics and/or volumetric parameters, ¹⁸F-FDG PET/CT textural features reflecting intratumor metabolic heterogeneity are useful for differentiating between uterine sarcoma and leiomyoma.

     

Mean and maximum standardized uptake values in [<Superscript>18</Superscript>F]FDG-PET for assessment of histopathological response in oesophageal squamous cell carcinoma or adenocarcinoma after radiochemotherapy

Purpose

To evaluate the potential of [¹⁸F]fluorodeoxyglucose positron emission tomography (FDG-PET) for the assessment of histopathological response and survival after neoadjuvant radiochemotherapy in patients with oesophageal cancer.

Patients and methods

In 2005 and 2006, 55 patients (43 men, 12 women; median age 60 years) with locally advanced oesophageal cancer (cT3-4 Nx M0; 24 with squamous cell carcinoma, 31 with adenocarcinoma) underwent transthoracic en bloc oesophagectomy after completion of treatment with cisplatin, 5-fluorouracil, and radiotherapy ad 36 Gy in a prospective clinical trial. Of the 55 patients, 21 (38%) were classified as histopathological responders (<10% vital residual tumour cells) and 34 (62%) as nonresponders. FDG-PET was performed before (PET 1) and 3–4 weeks after the end (PET 2) of radiochemotherapy with assessment of maximum and average standardized uptake values (SUV) for correlation with histopathological response and survival.

Results

Histopathological responders had a slightly higher baseline SUV than nonresponders (p<0.0001 between PET 1 and PET 2 for responders and nonresponders) and the decrease was more prominent in responders. Except for SUVmax in patients with squamous cell carcinoma neither baseline nor preoperative SUV nor percent SUV reduction correlated significantly with histopathological response. Histopathological responders had a 2-year overall survival of 91?±?9% and nonresponders a survival of 53?±?10% (p?=?0.007).

Conclusion

Our study does not support recent reports that FDG-PET predicts histopathological response and survival in patients with locally advanced oesophageal cancer treated by neoadjuvant radiochemotherapy.

     

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.

     

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.

     

A comparison of five partial volume correction methods for Tau and Amyloid PET imaging with [<Superscript>18</Superscript>F]THK5351 and [<Superscript>11</Superscript>C]PIB

Purpose

To suppress partial volume effect (PVE) in brain PET, there have been many algorithms proposed. However, each methodology has different property due to its assumption and algorithms. Our aim of this study was to investigate the difference among partial volume correction (PVC) method for tau and amyloid PET study.

Methods

We investigated two of the most commonly used PVC methods, Müller-Gärtner (MG) and geometric transfer matrix (GTM) and also other three methods for clinical tau and amyloid PET imaging. One healthy control (HC) and one Alzheimer’s disease (AD) PET studies of both [¹⁸F]THK5351 and [¹¹C]PIB were performed using a Eminence STARGATE scanner (Shimadzu Inc., Kyoto, Japan). All PET images were corrected for PVE by MG, GTM, Labbé (LABBE), Regional voxel-based (RBV), and Iterative Yang (IY) methods, with segmented or parcellated anatomical information processed by FreeSurfer, derived from individual MR images. PVC results of 5 algorithms were compared with the uncorrected data.

Results

In regions of high uptake of [¹⁸F]THK5351 and [¹¹C]PIB, different PVCs demonstrated different SUVRs. The degree of difference between PVE uncorrected and corrected depends on not only PVC algorithm but also type of tracer and subject condition.

Conclusion

Presented PVC methods are straight-forward to implement but the corrected images require careful interpretation as different methods result in different levels of recovery.

     

Intratumoral heterogeneity of <Superscript>18</Superscript>F-FDG uptake predicts survival in patients with pancreatic ductal adenocarcinoma

Purpose

To assess whether intratumoral heterogeneity measured by ¹⁸F-FDG PET texture analysis has potential as a prognostic imaging biomarker in patients with pancreatic ductal adenocarcinoma (PDAC).

Methods

We evaluated a cohort of 137 patients with newly diagnosed PDAC who underwent pretreatment ¹⁸F-FDG PET/CT from January 2008 to December 2010. First-order (histogram indices) and higher-order (grey-level run length, difference, size zone matrices) textural features of primary tumours were extracted by PET texture analysis. Conventional PET parameters including metabolic tumour volume (MTV), total lesion glycolysis (TLG), and standardized uptake value (SUV) were also measured. To assess and compare the predictive performance of imaging biomarkers, time-dependent receiver operating characteristic (ROC) curves for censored survival data and areas under the ROC curve (AUC) at 2 years after diagnosis were used. Associations between imaging biomarkers and overall survival were assessed using Cox proportional hazards regression models.

Results

The best imaging biomarker for overall survival prediction was first-order entropy (AUC?=?0.720), followed by TLG (AUC?=?0.697), MTV (AUC?=?0.692), and maximum SUV (AUC?=?0.625). After adjusting for age, sex, clinical stage, tumour size and serum CA19-9 level, multivariable Cox analysis demonstrated that higher entropy (hazard ratio, HR, 5.59; P?=?0.028) was independently associated with worse survival, whereas TLG (HR 0.98; P?=?0.875) was not an independent prognostic factor.

Conclusion

Intratumoral heterogeneity of ¹⁸F-FDG uptake measured by PET texture analysis is an independent predictor of survival along with tumour stage and serum CA19-9 level in patients with PDAC. In addition, first-order entropy as a measure of intratumoral metabolic heterogeneity is a better quantitative imaging biomarker of prognosis than conventional PET parameters.

     

The role of <Superscript>18</Superscript>F-fluorodeoxyglucose uptake of bone marrow on PET/CT in predicting clinical outcomes in non-small cell lung cancer patients treated with chemoradiotherapy

Objectives

This study aimed to assess the relationship between bone marrow (BM) FDG uptake on PET/CT and serum inflammatory markers and to evaluate the prognostic value of BM FDG uptake for predicting clinical outcomes in non-small cell lung cancer (NSCLC) patients.

Methods

One hundred and six NSCLC patients who underwent FDG PET/CT for staging work-up and received chemoradiotherapy were enrolled. Mean BM FDG uptake (BM SUV) and BM-to-liver uptake ratio (BLR) were measured, along with volumetric parameters of PET/CT. The relationship of BM SUV and BLR with hematologic parameters and serum inflammatory markers was evaluated. Prognostic values of BM SUV and BLR for predicting progression-free survival (PFS) and overall survival (OS) were assessed.

Results

BM SUV and BLR were significantly correlated with white blood cell count and C-reactive protein level. On univariate analysis, BLR was a significant prognostic factor for both PFS and OS. On multivariate analysis, TNM stage and BLR were independent prognostic factors for PFS, and only TNM stage was an independent prognostic factor for OS.

Conclusions

In NSCLC patients, FDG uptake of BM reflects the systemic inflammatory response and can be used as a biomarker to identify patients with poor prognosis.

Key Points

? Bone marrow FDG uptake is correlated with serum inflammatory markers. ? Bone marrow FDG uptake is an independent prognostic factor for progression-free survival. ? Bone marrow FDG uptake can provide information on predicting lung cancer progression.

     

Preclinical in vivo and in vitro comparison of the translocator protein PET ligands [<Superscript>18</Superscript>F]PBR102 and [<Superscript>18</Superscript>F]PBR111

Purpose

To determine the metabolic profiles of the translocator protein ligands PBR102 and PBR111 in rat and human microsomes and compare their in vivo binding and metabolite uptake in the brain of non-human primates (Papio hamadryas) using PET-CT.

Methods

In vitro metabolic profiles of PBR102 and PBR111 in rat and human liver microsomes were assessed by liquid chromatography–tandem mass spectrometry. [¹⁸F]PBR102 and [¹⁸F]PBR111 were prepared by nucleophilic substitution of their corresponding p-toluenesulfonyl precursors with [¹⁸F]fluoride. List mode PET-CT brain imaging with arterial blood sampling was performed in non-human primates. Blood plasma measurements and metabolite analysis, using solid-phase extraction, provided the metabolite profile and metabolite-corrected input functions for kinetic model fitting. Blocking and displacement PET-CT scans, using PK11195, were performed.

Results

Microsomal analyses identified the O-de-alkylated, hydroxylated and N-de-ethyl derivatives of PBR102 and PBR111 as the main metabolites. The O-de-alkylated compounds were the major metabolites in both species; human liver microsomes were less active than those from rat. Metabolic profiles in vivo in non-human primates and previously published rat experiments were consistent with the microsomal results. PET-CT studies showed that K₁ was similar for baseline and blocking studies for both radiotracers; V_T was reduced during the blocking study, suggesting low non-specific binding and lack of appreciable metabolite uptake in the brain.

Conclusions

[¹⁸F]PBR102 and [¹⁸F]PBR111 have distinct metabolic profiles in rat and non-human primates. Radiometabolites contributed to non-specific binding and confounded in vivo brain analysis of [¹⁸F]PBR102 in rodents; the impact in primates was less pronounced. Both [¹⁸F]PBR102 and [¹⁸F]PBR111 are suitable for PET imaging of TSPO in vivo. In vitro metabolite studies can be used to predict in vivo radioligand metabolism and can assist in the design and development of better radioligands.

     

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.

     

<Superscript>18</Superscript>F-FDG PET radiomics approaches: comparing and clustering features in cervical cancer

Objectives

The aims of our study were to find the textural features on ¹⁸F-FDG PET/CT which reflect the different histological architectures between cervical cancer subtypes and to make a visual assessment of the association between ¹⁸F-FDG PET textural features in cervical cancer.

Methods

Eighty-three cervical cancer patients [62 squamous cell carcinomas (SCCs) and 21 non-SCCs (NSCCs)] who had undergone pretreatment ¹⁸F-FDG PET/CT were enrolled. A texture analysis was performed on PET/CT images, from which 18 PET radiomics features were extracted including first-order features such as standardized uptake value (SUV), metabolic tumor volume (MTV) and total lesion glycolysis (TLG), second- and high-order textural features using SUV histogram, normalized gray-level co-occurrence matrix (NGLCM), and neighborhood gray-tone difference matrix, respectively. These features were compared between SCC and NSCC using a Bonferroni adjusted P value threshold of 0.0028 (0.05/18). To assess the association between PET features, a heat map analysis with hierarchical clustering, one of the radiomics approaches, was performed.

Results

Among 18 PET features, correlation, a second-order textural feature derived from NGLCM, was a stable parameter and it was the only feature which showed a robust trend toward significant difference between SCC and NSCC. Cervical SCC showed a higher correlation (0.70 ± 0.07) than NSCC (0.64 ± 0.07, P = 0.0030). The other PET features did not show any significant differences between SCC and NSCC. A higher correlation in SCC might reflect higher structural integrity and stronger spatial/linear relationship of cancer cells compared with NSCC. A heat map with a PET feature dendrogram clearly showed 5 distinct clusters, where correlation belonged to a cluster including MTV and TLG. However, the association between correlation and MTV/TLG was not strong. Correlation was a relatively independent PET feature in cervical cancer.

Conclusions

¹⁸F-FDG PET textural features might reflect the differences in histological architecture between cervical cancer subtypes. PET radiomics approaches reveal the association between PET features and will be useful for finding a single feature or a combination of features leading to precise diagnoses, potential prognostic models, and effective therapeutic strategies.

     

<Superscript>89</Superscript>Zr-Onartuzumab PET imaging of c-MET receptor dynamics

Purpose

c-MET and its ligand hepatocyte growth factor are often dysregulated in human cancers. Dynamic changes in c-MET expression occur and might predict drug efficacy or emergence of resistance. Noninvasive visualization of c-MET dynamics could therefore potentially guide c-MET-directed therapies. We investigated the feasibility of ⁸⁹Zr-labelled one-armed c-MET antibody onartuzumab PET for detecting relevant changes in c-MET levels induced by c-MET-mediated epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib resistance or heat shock protein-90 (HSP90) inhibitor NVP-AUY-922 treatment in human non-small-cell lung cancer (NSCLC) xenografts.

Methods

In vitro membrane c-MET levels were determined by flow cytometry. HCC827ErlRes, an erlotinib-resistant clone with c-MET upregulation, was generated from the exon-19 EGFR-mutant human NSCLC cell line HCC827. Mice bearing HCC827 and HCC827ErlRes tumours in opposite flanks underwent ⁸⁹Zr-onartuzumab PET scans. The HCC827-xenografted mice underwent ⁸⁹Zr-onartuzumab PET scans before treatment and while receiving biweekly intraperitoneal injections of 100 mg/kg NVP-AUY-922 or vehicle. Ex vivo, tumour c-MET immunohistochemistry was correlated with the imaging results.

Results

In vitro, membrane c-MET was upregulated in HCC827ErlRes tumours by 213?±?44% in relation to the level in HCC827 tumours, while c-MET was downregulated by 69?±?9% in HCC827 tumours following treatment with NVP-AUY-922. In vivo, ⁸⁹Zr-onartuzumab uptake was 26% higher (P?<?0.05) in erlotinib-resistant HCC827ErlRes than in HCC827 xenografts, while HCC827 tumour uptake was 33% lower (P?<?0.001) following NVP-AUY-922 treatment.

Conclusion

The results show that ⁸⁹Zr-onartuzumab PET effectively discriminates relevant changes in c-MET levels and could potentially be used clinically to monitor c-MET status.

     

Therapy assessment of bone metastatic disease in the era of <Superscript>223</Superscript>radium

Purpose

Defining an optimal imaging modality for assessment of therapy and the best time of evaluation are pivotal for ideal patient’s management.

Methods

²²³Ra (Xofigo®, formerly Alpharadin) has been approved by the FDA and European Medicines Agency for treatment of metastatic castration-resistant prostate cancer with painful osseous involvement.

Results

PET/CT imaging using various radiotracers such as ¹⁸F–FDG, ¹⁸F–FCH, ⁶⁸Ga-PSMA and ¹⁸F–NaF have been investigated to mitigate the limitations of conventional imaging modalities. Diagnostic radiotracers that have properties similar to a therapeutic radiotracer will precisely assess of the possibility and efficacy of a treatment; this is the theranostic concept. An example of a diagnostic test employed for selecting targeted therapy is the combined use of ¹⁸F–fluoride PET/CT for evaluation of possible therapy with ²²³Ra.

Conclusion

This review examines the most recent publications related to this topic.

     

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.

     

Diagnostic accuracy of <Superscript>11</Superscript>C-methionine PET in detecting neuropathologically confirmed recurrent brain tumor after radiation therapy

Objective

This study aims to determine the diagnostic test accuracy (DTA) of ¹¹C-methionine (MET) PET in the discrimination between recurrent tumor and radiation-induced injury in neuropathologically confirmed cases.

Methods

A retrospective cohort of 30 patients with previously irradiated intracranial tumors (23 gliomas, 6 metastases, and 1 meningioma) was included. All patients underwent a preoperative MET PET and postoperative neuropathological analysis. Maximum and mean standardized uptake values (SUV) were obtained in the lesion, in the contralateral mirror region, and in the contralateral frontal cortex. Lesion-to-background SUV ratios (SUR mirror and SUR cortex) were then calculated. The Mann–Whitney U test was used to evaluate differences in SUV ratios between confirmed recurrent tumor and radiation injury. DTA was determined through receiver operating characteristic (ROC) analysis.

Results

Twenty-one patients had recurrent tumor and nine had radiation injury. The area under the ROC curve (AUC) was 0.89 for SUR_maxmirror and 0.88 for SUR_maxcortex. The mean (SD) of SUR_maxmirror was 2.37 (0.58) in tumor recurrence and 1.57 (0.40) in radiation necrosis (P?≤?0.001). The corresponding values for SUR_maxcortex were 2.13 (0.50) and 1.45 (0.37) (P?=?0.001). Clinically relevant cutoffs were SUR_maxmirror ≥?1.99 giving a specificity of 100% for tumor recurrence with a sensitivity of 76% and SUR_maxcortex ≥?1.58 giving a sensitivity and specificity of 90 and 78%, respectively.

Conclusions

Based on neuropathologically confirmed cases, the DTA of SUR_maxmirror and SUR_maxcortex from ¹¹C-methionine PET was high when discriminating recurrent tumor from radiation injury.

     

Molecular imaging of cholinergic processes in prostate cancer using <Superscript>11</Superscript>C-donepezil and <Superscript>18</Superscript>F-FEOBV

Purpose

High-grade prostate cancer (PC) displays parasympathetic neoneurogenesis. We investigated the binding of two PET tracers that visualize cholinergic nerves in PC tissue using autoradiography.

Methods

Prostatectomy tissue was subjected to autoradiography with ¹¹C-donepezil and ¹⁸F-FEOBV and correlated with Gleason scores (GS). Regions of interest on the autoradiograms were defined and quantified. Tracer binding in cancer tissue regions was compared with that in normal tissue.

Results

We included 13 patients with biopsy-verified PC. In particular, ¹¹C-donepezil uptake was higher in “high-grade” PC (GS ≥4?+?3) than in “low-grade” PC and benign hyperplasia. ¹¹C-donepezil uptake ranged from a mean of 56 % higher (GS 3?+?3) to 409 % higher (GS 4?+?4), and ¹⁸F-FEOBV uptake ranged from 67 % higher (GS 3?+?3) to 194 % higher (GS 4?+?5). The uptake of both tracers was higher in PC with a high GS than in PC with a low GS, but the difference was significant only for ¹¹C-donepezil (p?=?0.003).

Conclusion

Uptake of PET tracers binding to cholinergic nerves was markedly higher in PC with a high GS than in PC with a low GS. This finding implies that ¹¹C-donepezil PET/CT may be able to differentiate between low-grade and high-grade PC.

     

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

Objective

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

Methods

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

Results

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

Conclusion

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

     

<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.