Clinical evaluation of whole-body oncologic PET with time-of-flight and point-spread function for the hybrid PET/MR system

PurposeHybrid positron emission tomography/magnetic resonance (PET/MR) imaging is a new multimodality imaging technology that can provide structural and functional information simultaneously. The aim of this study was to investigate the effects of the time-of-flight (TOF) and point-spread function (PSF) on small lesions observed in PET/MR images from clinical patient image sets.Materials and methodsThis study evaluated 54 small lesions in 14 patients who had undergone ¹⁸F-fluorodeoxyglucose (FDG) PET/MR. Lesions up to 30 mm in diameter were included. The PET data were reconstructed with a baseline ordered-subsets expectation-maximization (OSEM) algorithm, OSEM + PSF, OSEM + TOF and OSEM + TOF + PSF. PET image quality and small lesions were visually evaluated and scored by a 3-point scale. A quantitative analysis was then performed using the mean and maximum standardized uptake value (SUV) of the small lesions (SUV_mean and SUV_max). The lesions were divided into two groups according to the long-axis diameter and the location respectively and evaluated with each reconstruction algorithm. We also evaluated the background signal by analyzing the SUV_liver.ResultsOSEM + TOF + PSF provided the highest value and OSEM + TOF or PSF showed a higher value than OSEM for the visual assessment and quantitative analysis. The combination of TOF and PSF increased the SUV_mean by 26.6% and the SUV_max by 30.0%. The SUV_liverwas not influenced by PSF or TOF. For the OSEM + TOF + PSF model, the change in SUV_mean and SUV_max for lesions <10 mm in diameter was 31.9% and 35.8%, and 24.5% and 27.6% for lesions 10–30 mm in diameter, respectively. The abdominal lesions obtained the higher SUV than those of chest on the images with TOF and/or PSF.ConclusionApplication of TOF and PSF significantly increased the SUV of small lesions in hybrid PET/MR images, potentially improving small lesion detectability.     

Improved clinical workflow for simultaneous whole-body PET/MRI using high-resolution CAIPIRINHA-accelerated MR-based attenuation correction

PurposeTo explore the value and reproducibility of a novel magnetic resonance based attenuation correction (MRAC) using a CAIPIRINHA-accelerated T1-weighted Dixon 3D-VIBE sequence for whole-body PET/MRI compared to the clinical standard.MethodsThe PET raw data of 19 patients from clinical routine were reconstructed with standard MRAC (MRAC_std) and the novel MRAC (MRAC_caipi), a prototype CAIPIRINHA accelerated Dixon 3D-VIBE sequence, both acquired in 19 s/bed position. Volume of interests (VOIs) for liver, lung and all voxels of the total image stack were created to calculate standardized uptake values (SUV_mean) followed by inter-method agreement (Passing-Bablok regression, Bland-Altman analysis). A voxel-wise SUV comparison per patient was performed for intra-individual correlation between MRAC_std and MRAC_caipi. Difference images (MRAC_std-MRAC_caipi) of attenuation maps and SUV images were calculated. The image quality of in/opposed-phase water and fat images obtained from MRAC_caipi was assessed by two readers on a 5-point Likert-scale including intra-class coefficients for inter-reader agreement.ResultsSUV_mean correlations of VOIs demonstrated high linearity (0.95 < Spearman’s rho < 1, p < 0.0001, respectively), substantiated by voxel-wise SUV scatter-plots (1.79 × 10⁸ pixels). Outliers could be explained by different physiological conditions between the scans such as different segmentation of air-containing tissue, lungs, kidneys, metal implants, diaphragm edge or small air bubbles in the gastrointestinal tracts that moved between MRAC acquisitions. Nasal sinuses and the trachea were better segmented in MRAC_caipi. High-resolution T1w Dixon 3D VIBE images were acquired in all cases and could be used for PET/MRI fusion. MRAC_caipi images were of high diagnostic quality (4.2 ± 0.8) with 0.92-0.96 intra-class correlation.ConclusionsThe novel prototype MRAC_caipi extends the value for attenuation correction by providing a high spatial resolution DIXON-based dataset suited for diagnostic assessment towards time-efficient whole-body PET/MRI.     

Role of pharmacokinetic parameters derived with high temporal resolution DCE MRI using simultaneous PET/MRI system in breast cancer: A feasibility study

PurposeTo evaluate the reliability of pharmacokinetic parameters like K^trans, Kep and v_e derived through DCE MRI breast protocol using 3 T Simultaneous PET/MRI (3 Tesla Positron Emission Tomography/Magnetic Resonance Imaging) system in distinguishing benign and malignant lesions.Materials and methodsHigh temporal resolution DCE (Dynamic Contrast Enhancement) MRI performed as routine breast MRI for diagnosis or as a part of PET/MRI for cancer staging using a 3 T simultaneous PET/MRI system in 98 women having 109 breast lesions were analyzed for calculation of pharmacokinetic parameters (K^trans, v_e, and Kep) at 60 s time point using an in-house developed computation scheme.ResultsReceiver operating characteristic (ROC) curve analysis revealed a cut off value for K^trans, Kep, v_e as 0.50, 2.59, 0.15 respectively which reliably distinguished benign and malignant breast lesions. Data analysis revealed an overall accuracy of 94.50%, 79.82% and 87.16% for K^trans, Kep, v_e respectively. Introduction of native T1 normalization with an externally placed phantom showed a higher accuracy (94.50%) than without native T1 normalization (93.50%) with an increase in specificity of 87% vs 84%.ConclusionOverall the results indicate that reliable measurement of pharmacokinetic parameters with reduced acquisition time is feasible in a 3TMRI embedded PET/MRI system with reasonable accuracy and application may be extended to exploit the potential of simultaneous PET/MRI in further work on breast cancer.     

Dynamic contrast-enhanced perfusion area-detector CT assessed with various mathematical models: Its capability for therapeutic outcome prediction for non-small cell lung cancer patients with chemoradiotherapy as compared with that of FDG-PET/CT

PurposeTo directly compare the capability of dynamic first-pass contrast-enhanced (CE-) perfusion area-detector CT (ADCT) and PET/CT for early prediction of treatment response, disease progression and overall survival of non-small cell carcinoma (NSCLC) patients treated with chemoradiotherapy.Materials and methodsFifty-three consecutive Stage IIIB NSCLC patients who had undergone PET/CT, dynamic first-pass CE-perfusion ADCT, chemoradiotherapy, and follow-up examination were enrolled in this study. They were divided into two groups: 1) complete or partial response (CR + PR) and 2) stable or progressive disease (SD + PD). Pulmonary arterial and systemic arterial perfusions and total perfusion were assessed at targeted lesions with the dual-input maximum slope method, permeability surface and distribution volume with the Patlak plot method, tumor perfusion with the single-input maximum slope method, and SUV_max, and results were averaged to determine final values for each patient. Next, step-wise regression analysis was used to determine which indices were the most useful for predicting therapeutic effect. Finally, overall survival of responders and non-responders assessed by using the indices that had a significant effect on prediction of therapeutic outcome was statistically compared.ResultsThe step-wise regression test showed that therapeutic effect (r² = 0.63, p = 0.01) was significantly affected by the following three factors in order of magnitude of impact: systemic arterial perfusion, total perfusion, and SUV_max. Mean overall survival showed a significant difference for total perfusion (p = 0.003) and systemic arterial perfusion (p = 0.04).ConclusionDynamic first-pass CE-perfusion ADCT as well as PET/CT are useful for treatment response prediction in NSCLC patients treated with chemoradiotherapy.     

Assessment of treatment response after lung stereotactic body radiotherapy using diffusion weighted magnetic resonance imaging and positron emission tomography: A pilot study

Background and purposeThere is no early predictor of treatment response after lung stereotactic body radiotherapy (SBRT). We conducted this pilot study to evaluate whether serial diffusion weighted magnetic resonance imaging (DW-MRI) or positron emission tomography (PET) could predict response after SBRT.Material and methodsEarly stage non-small cell lung cancer patients who received SBRT were eligible. DW-MRI and PET were undertaken pretreatment and every 3 months after SBRT in the first year. Patients with <1 year of follow-up were excluded from the analysis. The apparent diffusion coefficient (ADC) value and maximum standardized uptake value (SUV_max) of tumors were measured and compared between groups with or without local recurrence (LR).ResultsFifteen patients were enrolled and the data of 14 patients were analyzed. The median ADC value was significantly lower in patients with LR (n = 3) than in those without LR (n = 11) at 3 and 6 months (1.11 vs. 1.54 and 0.98 vs. 1.69 [×10⁻³ mm²/s]; p = 0.039 and 0.012, respectively) while there was no significant difference pretreatment and at 9 and 12 months after treatment. No significant difference was observed in the SUV_max at any time point.ConclusionsDW-MRI could be an early predictor of treatment response after lung SBRT.     

Impact of blood glucose,diabetes, insulin,and obesity on standardized uptake values in tumors and healthy organs on 18F-FDG PET/CT

IntroductionChronically altered glucose metabolism interferes with ¹⁸F-FDG uptake in malignant tissue and healthy organs and may therefore lower tumor detection in ¹⁸F-FDG PET/CT. The present study assesses the impact of elevated blood glucose levels (BGL), diabetes, insulin treatment, and obesity on ¹⁸F-FDG uptake in tumors and biodistribution in normal organ tissues.Methods¹⁸F-FDG PET/CT was analyzed in 90 patients with BGL ranging from 50 to 372 mg/dl. Of those, 29 patients were diabetic and 21 patients had received insulin prior to PET/CT; 28 patients were obese with a body mass index > 25. The maximum standardized uptake value (SUV_max) of normal organs and the main tumor site was measured. Differences in SUV_max in patients with and without elevated BGLs, diabetes, insulin treatment, and obesity were compared and analyzed for statistical significance.ResultsIncreased BGLs were associated with decreased cerebral FDG uptake and increased uptake in skeletal muscle. Diabetes and insulin diminished this effect, whereas obesity slightly enhanced the outcome. Diabetes and insulin also increased the average SUV_max in muscle cells and fat, whereas the mean cerebral SUV_max was reduced. Obesity decreased tracer uptake in several healthy organs by up to 30%. Tumoral uptake was not significantly influenced by BGL, diabetes, insulin, or obesity.ConclusionsChanges in BGLs, diabetes, insulin, and obesity affect the FDG biodistribution in muscular tissue and the brain. Although tumoral uptake is not significantly impaired, these findings may influence the tumor detection rate and are therefore essential for diagnosis and follow-up of malignant diseases.     

PET quantification with a histogram derived total activity metric: Superior quantitative consistency compared to total lesion glycolysis with absolute or relative SUV thresholds in phantoms and lung cancer patients

IntroductionThe increasing use of molecular imaging probes as biomarkers in oncology emphasizes the need for robust and stable methods for quantifying tracer uptake in PET imaging. The primary motivation for this research was to find an accurate method to quantify the total tumor uptake. Therefore we developed a histogram-based method to calculate the background subtracted lesion (BSL) activity and validated BSL by comparing the quantitative consistency with the total lesion glycolysis (TLG) in phantom and patient studies.MethodsA thorax phantom and a PET-ACR quality assurance phantom were scanned with increasing FDG concentrations. Volumes of interest (VOIs) were placed over each chamber. TLG was calculated with a fixed threshold at SUV 2.5 (TLG_2.5) and a relative threshold at 42% of SUV_max (TLG_42%). The histogram for each VOI was built and BSL was calculated. Comparison with the total injected FDG activity (TIA) was performed using concordance correlation coefficients (CCC) and the slope (a). Fifty consecutive patients with FDG-avid lung tumors were selected under an IRB waiver. TLG_42%, TLG_2.5 and BSL were compared to the reference standard calculating CCC and the slope.ResultsIn both phantoms, the CCC for lesions with a TIA ≤ 50 ml*SUV between TIA and BSL was higher and the slope closer to 1 (CCC = 0.933, a = 1.189), than for TLG_42% (CCC = 0.350, a = 0.731) or TLG_2.5 (CCC = 0.761, a = 0.727). In 50 lung lesions BSL had a slope closer to 1 compared to the reference activity than TLG_42% (a = 1.084 vs 0.618 – for high activity lesions) and also closer to 1 than TLG_2.5 (a = 1.117 vs 0.548 – for low activity lesions).ConclusionThe histogram based BSL correlated better with TIA in both phantom studies than TLG_2.5 or TLG_42%. Also in lung tumors, the BSL activity is overall more accurate in quantifying the lesion activity compared to the two most commonly applied TLG quantification methods.     

Differentiation and diagnosis of benign and malignant testicular lesions using 18F-FDG PET/CT

ObjectivesThe purpose of this study was to evaluate the differential diagnostic value of ¹⁸F-fluorodeoxy glucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) for benign and malignant testicular lesions.MethodsThe PET/CT scans of 53 patients with testicular lesions confirmed by biopsy or surgical pathology were retrospectively analyzed. There were 32 cases of malignant tumors and 21 cases of benign lesions. Differences in the maximum standardized uptake value (SUVmax) measurements and the SUVmax lesion/background ratios between benign and malignant lesions were analyzed. The diagnostic value of this PET/CT modality for the differential diagnosis of benign versus malignant testicular lesions was calculated.ResultsThe differences in the SUVmax measurements and the SUVmax lesion/background ratios between benign and malignant lesions were statistically significant (SUVmax: Z = −4.295, p = 0.000; SUVmax lesion/background ratio: Z = −5.219, p = 0.000); specifically, both of these indicators were higher in malignant lesions compared to benign lesions. An SUVmax of 3.75 was the optimal cutoff value to differentiate between benign and malignant testicular lesions. The diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of this PET/CT modality in the differential diagnosis of benign versus malignant testicular lesions were 90.6%, 80.9%, 86.8%, 87.9%, and 85.0%, respectively.Conclusions¹⁸F-FDG PET/CT can accurately identify benign and malignant testicular lesions.     

Association of pharmacokinetic and metabolic parameters derived using simultaneous PET/MRI: Initial findings and impact on response evaluation in breast cancer

PurposeTo study relationships among pharmacokinetic and ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET parameters obtained through simultaneous PET/MRI in breast cancer patients and evaluate their combined potential for response evaluation.MethodsThe study included 41 breast cancer patients for correlation study and 9 patients (pre and post therapy) for response evaluation. All patients underwent simultaneous PET/MRI with dedicated breast imaging. Pharmacokinetic parameters and PET parameters for tumor were derived using an in- house developed and vendor provided softwares respectively. Relationships between SUV and pharmacokinetic parameters and clinical as well as histopathologic parameters were evaluated using Spearman correlation analysis. Response to chemotherapy was derived as percentage reduction in size and in parameters post therapy.ResultsSignificant correlations were observed between SUVmean, max, peak, TLG with K^trans (ρ = 0.446, 0.417, 0.491, 0.430; p ≤ 0.01); with Kep(ρ = 0.303, ρ = 0.315, ρ = 0.319; p ≤ 0.05); and with iAUC(ρ = 0.401, ρ = 0.410, ρ = 0.379; p ≤ 0.05, p ≤ 0.01). The ratio of ve/iAUC showed significant negative correlation to SUVmean, max, peak and TLG (ρ = 0.420, 0.446, 0.443, 0.426; p ≤ 0.01). Ability of SUV as well as pharmacokinetic parameters to predict response to therapy matched the RECIST criteria in 9 out of 11 lesions in 9 patients. Maximum post therapy quantitative reduction was observed in SUVpeak, TLG and K^trans.ConclusionSimultaneous PET/MRI enables illustration of close interactions between glucose metabolism and pharmacokinetic parameters in breast cancer patients and potential of their simultaneity in response assessment to therapy.     

F-18 FDG PET/CT metabolic tumor volume predicts overall survival in patients with disseminated epithelial ovarian cancer

ObjectiveWe evaluated the prognostic impact of quantitative assessment by maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV) and tumour lesion glycolysis (TLG) on [F-18] FDG PET/CT for patients with peritoneal carcinomatosis from epithelial ovarian cancer (EOC).MethodsThirty-one patients with EOC underwent PET/CT for an early restaging after cytoreductive surgery, having been diagnosed with carcinomatosis (before chemotherapy). The SUVmax, MTV (cm³; 42% threshold) and TLG (g) were registered on residual peritoneal lesions. The patients were followed up 20 ± 12 months thereafter. The PET/CT results were compared to overall survival (OS).ResultsThe Kaplan-Meier survival analysis for the SUVmax did not reveal significant differences in OS (p = 0.48). The MTV survival analysis showed a significant higher OS in patients presenting with a higher tumour burden than those with less tumour burden (p = 0.01; 26 vs. 14 months), whereas TLG exhibited a similar trend though not significant (p = 0.06). Apart from chemo-resistance, the higher the MTV, the better will be the response to chemotherapy.ConclusionsQuantitative assessment by MTV rather than by SUVmax and TLG on PET/CT may be helpful for stratifying patients who present with peritoneal carcinomatosis from EOC, in order to implement the appropriate therapeutic regimen.     

Influence of PET reconstruction technique and matrix size on qualitative and quantitative assessment of lung lesions on [18F]-FDG-PET: A prospective study in 37 cancer patients

PurposeTo evaluate the influence of point spread function (PSF)-based reconstruction and matrix size for PET on (1) lung lesion detection and (2) standardized uptake values (SUV).MethodsThis prospective study included oncological patients who underwent [18F]-FDG-PET/CT for staging. PET data were reconstructed with a 2D ordered subset expectation maximization (OSEM) algorithm, and a 2D PSF-based algorithm (TrueX), separately with two matrix sizes (168 × 168 and 336 × 336). The four PET reconstructions (TrueX-168; OSEM-168; TrueX-336; and OSEM-336) were read independently by two raters, and PET-positive lung lesions were recorded. Blinded to the PET findings, a third independent rater assessed lung lesions with diameters of >4 mm on CT. Subsequently, PET and CT were reviewed side-by side in consensus. Multi-factorial logistic regression analyses and two-way repeated measures analyses of variance (ANOVA) were performed.ResultsThirty-seven patients with 206 lung lesions were included. Lesion-based PET sensitivities differed significantly between reconstruction algorithms (P < 0.001) and between reconstruction matrices (P = 0.022). Sensitivities were 94.2% and 88.3% for TrueX-336; 88.3% and 85.9% for TrueX-168; 67.8% and 66.3% for OSEM-336; and 67.0% and 67.9% for OSEM-168; for rater 1 and rater 2, respectively. SUV_max and SUV_mean were significantly higher for images reconstructed with 336 × 336 matrices than for those reconstructed with 168 × 168 matrices (P < 0.001).ConclusionOur results demonstrate that PSF-based PET reconstruction, and, to a lesser degree, higher matrix size, improve detection of metabolically active lung lesions. However, PSF-based PET reconstructions and larger matrix sizes lead to higher SUVs, which may be a concern when PET data from different institutions are compared.     

Single-step radiosynthesis and in vivo evaluation of a novel fluorine-18 labeled hippurate for use as a PET renal agent

ObjectiveThe objective of this study was to investigate a new fluorine-18 labeled hippurate, m-cyano-p-[¹⁸ F]fluorohippurate ([¹⁸ F]CNPFH), as a potential radiopharmaceutical for evaluating renal function by PET.Methods[¹⁸ F]CNPFH was synthesized by a direct one-step nucleophilic aromatic substitution using an ¹⁸ F-for-[N(CH₃)₃]⁺-reaction. In vivo stability was determined by HPLC analysis of urine collected from a healthy rat at 30 min p.i. of [¹⁸ F]CNPFH. The plasma protein binding (PPB) and erythrocyte uptake of [¹⁸ F]CNPFH were determined using blood collected from healthy rats at 5 min p.i. Biodistribution studies were conducted in healthy rats at 10 min and 1 h p.i. of [¹⁸ F]CNPFH. Dynamic PET/CT imaging data were acquired in normal rats. For comparison, the same rats underwent an identical imaging study using the previously reported p-[¹⁸ F]fluorohippurate ([¹⁸ F]PFH) renal agent.Results[¹⁸ F]CNPFH demonstrated high in vivo stability with no metabolic degradation. The in vivo PPB and erythrocyte uptake of [¹⁸ F]CNPFH were found to be comparable to those of [¹⁸ F]PFH. Biodistribution and dynamic PET/CT imaging studies revealed a rapid clearance of [¹⁸ F]CNPFH primarily through the renal–urinary pathway. However, unlike [¹⁸ F]PFH, a minor (about 12%) fraction was eliminated via the hepatobiliary route. The PET-derived [¹⁸ F]CNPFH renograms revealed an average time-to-peak (T_max) of 3.2 ± 0.4 min which was similar to [¹⁸ F]PFH, but the average time-to-half-maximal activity (11.4 ± 2.8 min) was found to be higher than that of [¹⁸ F]PFH (7.1 ± 1.3 min).ConclusionsOur in vivo results indicate that [¹⁸ F]CNPFH has renogram characteristics similar to those of [¹⁸ F]PFH, however, the unexpected hepatobiliary elimination is adding undesirable background signal in the PET images.     

Hepatic steatosis is associated with increased hepatic FDG uptake

ObjectiveThe use of liver as a reference tissue for semi-quantification of tumour FDG uptake may not be valid in hepatic steatosis (HS). Previous studies on the relation between liver FDG uptake and HS have been contradictory probably because they ignored blood glucose (BG). Because hepatocyte and blood FDG concentrations equalize, liver FDG uptake parallels BG, which must therefore be considered when studying hepatic FDG uptake. We therefore re-examined the relation between HS and liver uptake taking BG into account.MethodsThis was a retrospective study of 304 patients undergoing routine PET/CT with imaging 60 min post-FDG. Average standard uptake value (SUV_ave), maximum SUV (SUV_max) and CT density (index of HS) were measured in a liver ROI. Blood pool SUV was based on the left ventricular cavity (SUV_LV). Correlations were assessed using least squares fitting of continuous data. Patients were also divided into BG subgroups (<4, 4–5, 5–6, 6–8, 8–10 and 10+ mmol/l).ResultsSUV_ave, SUV_max and SUV_LV displayed similar relations with BG. SUV_max/SUV_LV, but not SUV_ave/SUV_LV, correlated significantly with BG. SUV_max, but not SUV_ave, correlated inversely with CT density before and after adjusting for BG. SUV_max/SUV_ave correlated more strongly with CT density than SUV_max. CT density correlated inversely with SUV_max/SUV_LV but positively with SUV_ave/SUV_LV.ConclusionsHepatic SUV is more influenced by BG than by HS. Its relation with BG renders it unsuitable as a reference tissue. Nevertheless, hepatic fat does correlate positively with liver SUV, although this is seen only with SUV_max because SUV_ave is ‘diluted’ by hepatic fat.     

Synthesis and evaluation of 2-amino-5-(4-[18F]fluorophenyl)pent-4-ynoic acid ([18F]FPhPA): A novel 18F-labeled amino acid for oncologic PET imaging

Introduction¹⁸ F-labeled amino acids are important PET radiotracers for molecular imaging of cancer. This study describes synthesis and radiopharmacological evaluation of 2-amino-5-(4-[¹⁸ F]fluorophenyl)pent-4-ynoic acid ([¹⁸ F]FPhPA) as a novel amino acid radiotracer for oncologic imaging.Methods¹⁸ F]FPhPA was prepared using Pd-mediated Sonogashira cross-coupling reaction between 4-[¹⁸ F]fluoroiodobenzene ([¹⁸ F]FIB) and propargylglycine. The radiopharmacological profile of [¹⁸ F]FPhPA was evaluated in comparison with O-(2-[¹⁸ F]fluoroethyl)-L-tyrosine ([¹⁸ F]FET) using the murine breast cancer cell line EMT6 involving cellular uptake studies, radiotracer uptake competitive inhibition experiments and small animal PET imaging.Results¹⁸ F]FPhPA was prepared in 42 ± 10% decay-corrected radiochemical yield with high radiochemical purity >95% after semi-preparative HPLC purification. Cellular uptake of L-[¹⁸ F]FPhPA reached a maximum of 58 ± 14 % radioactivity/mg protein at 90 min. Lower uptake was observed for racemic and D-[¹⁸ F]FPhPA.Radiotracer uptake inhibition studies by synthetic and naturally occurring amino acids suggested that Na⁺-dependent system ASC, especially ASCT2, and Na⁺-independent system L are important amino acid transporters for [¹⁸ F]FPhPA uptake into EMT6 cells. Small animal PET studies demonstrated similar high tumor uptake of [¹⁸ F]FPhPA in EMT6 tumor-bearing mice compared to [¹⁸ F]FET reaching a maximum standardized uptake value (SUV) of 1.35 after 60 min p.i.. Muscle uptake of [¹⁸ F]FPhPA was higher (SUV_30min = 0.65) compared to [¹⁸ F]FET (SUV_30min = 0.40), whereas [¹⁸ F]FPhPA showed a more rapid uptake and clearance from the brain compared to [¹⁸ F]FET.ConclusionL-[¹⁸ F]FPhPA is the first ¹⁸ F-labeled amino acid prepared through Pd-mediated cross-coupling reaction.Advances in Knowledge and Implications for patient CareL-[¹⁸ F]FPhPA displayed promising properties as a novel amino acid radiotracer for molecular imaging of system ASC and system L amino acid transporters in cancer.     

Evaluation of PET and MR datasets in integrated 18F-FDG PET/MRI: A comparison of different MR sequences for whole-body restaging of breast cancer patients

ObjectivesTo investigate the diagnostic value of different MR sequences and 18F-FDG PET data for whole-body restaging of breast cancer patients utilizing PET/MRI.MethodsA total of 36 patients with suspected tumor recurrence of breast cancer based on clinical follow-up or abnormal findings in follow-up examinations (e.g. CT, MRI) were prospectively enrolled in this study. All patients underwent a PET/CT and subsequently an additional PET/MR scan. Two readers were instructed to identify the occurrence of a tumor relapse in subsequent MR and PET/MR readings, utilizing different MR sequence constellations for each session. The diagnostic confidence for the determination of a malignant or benign lesion was qualitatively rated (3-point ordinal scale) for each lesion in the different reading sessions and the lesion conspicuity (4-point ordinal scale) for the three different MR sequences was additionally evaluated.ResultsTumor recurrence was present in 25/36 (69%) patients. All three PET/MRI readings showed a significantly higher accuracy as well as higher confidence levels for the detection of recurrent breast cancer lesions when compared to MRI alone (p < 0.05). Furthermore, all three PET/MR sequence constellations showed comparable diagnostic accuracy for the identification of a breast cancer recurrence (p > 0.05), yet the highest confidence levels were obtained, when all three MR sequences were used for image interpretation. Moreover, contrast-enhanced T1-weighted VIBE imaging showed significantly higher values for the delineation of malignant and benign lesions when compared to T2 w HASTE and diffusion-weighted imaging.ConclusionIntegrated PET/MRI provides superior restaging of breast cancer patients over MRI alone. Facing the need for appropriate and efficient whole-body PET/MR protocols, our results show the feasibility of fast and morphologically adequate PET/MR protocols. However, considering an equivalent accuracy for the detection of breast cancer recurrences in the three PET/MR readings, the application of contrast-agent and the inclusion of DWI in the study protocol seems to be debatable.     

Determination of optimal acquisition time of [18F]FCWAY PET for imaging serotonin 1A receptors in the healthy male subjects

The purpose of this research is to find optimal acquisition time point of [¹⁸F]FCWAY PET for the assessment of serotonin 1A receptor (5-HT_1A) density. To achieve this goal, we examined the specific-to-nonspecific ratios in various brain regions. The cerebellum has very few 5-HT_1A receptors in the brain, so we set this region as the reference tissue. As a result, specific-to-nonspecific binding ratios in the frontal, temporal cortex and the hippocampus were steadily increased at 90 min after injection and remained stable at 120 min. In addition, the binding ratio of the late time was significantly higher than that of the previous time points. From these results, we recommend that 90 min p.i. is a better single time point for the analysis rather than previous time points for assessing [¹⁸F]FCWAY binding to 5-HT_1A receptors.     

Analysis of [11C]methyl-candesartan kinetics in the rat kidney for the assessment of angiotensin II type 1 receptor density in vivo with PET

IntroductionAngiotensin II type 1 (AT₁) receptors play a key role in the regulation of renal and cardiovascular functions and have been implicated in the pathogenesis of many diseases. The aim of this study was to assess binding of the novel radioligand [¹¹C]methyl-candesartan to AT₁ receptors in the rat kidney in vivo with PET.MethodsDynamic PET images were acquired for 60 min at baseline, with coinjection of candesartan (5 mg/kg), and after injection of PD123,319 (5 mg/kg). Volumes of distribution (R_C? V_T) were estimated with a two-compartment model, by Logan analysis, and by taking the tissue-to-plasma activity ratio at 50–60 min post-injection.ResultsThe two-compartment model did not describe the kinetics at baseline adequately and the baseline scans were too short to obtain accurate estimates of R_C? V_T with the Logan approach. Based on the tissue-to-plasma ratios, roughly one-third of V_T at baseline could be attributed to AT₁ receptor binding. There were no indications of AT₂ receptor binding in the rat kidney.ConclusionIt may be possible to detect changes in AT₁ receptor density in the rat kidney in vivo with [¹¹C]methyl-candesartan and PET. Imaging AT₁ receptors with PET may provide valuable information on the role of these receptors in the pathogenesis of diseases such as hypertension, diabetic nephropathy, ventricular remodeling, and heart failure.     

Adrenergic pathway activation enhances brown adipose tissue metabolism: A [18 F]FDG PET/CT study in mice

ObjectivePharmacologic approaches to study brown adipocyte activation in vivo with a potential of being translational to humans are desired. The aim of this study was to examine pre- and postsynaptic targeting of adrenergic system for enhancing brown adipose tissue (BAT) metabolism quantifiable by [¹⁸ F]fluoro-2-deoxyglucose ([¹⁸ F]FDG) positron emission tomography (PET)/computed tomography (CT) in mice.MethodsA β₃-adrenoreceptor selective agonist (CL 316243), an adenylyl cyclase enzyme activator (forskolin) and a potent blocker of presynaptic norepinephrine transporter (atomoxetine), were injected through the tail vein of Swiss Webster mice 30 minutes before intravenous (iv) administration of [¹⁸ F]FDG. The mice were placed on the PET/CT bed for 30 min PET acquisition followed by 10 min CT acquisition for attenuation correction and anatomical delineation of PET images.ResultsActivated interscapular (IBAT), cervical, periaortic and intercostal BAT were observed in 3-dimentional analysis of [¹⁸ F]FDG PET images. CL 316243 increased the total [¹⁸ F]FDG standard uptake value (SUV) of IBAT 5-fold greater compared to that in placebo-treated mice. It also increased the [¹⁸ F]FDG SUV of white adipose tissue (2.4-fold), and muscle (2.7-fold), as compared to the control. There was no significant difference in heart, brain, spleen and liver uptakes between groups. Forskolin increased [¹⁸ F]FDG SUV of IBAT 1.9-fold greater than that in placebo-treated mice. It also increased the [¹⁸ F]FDG SUV of white adipose tissue (2.2-fold) and heart (5.4-fold) compared to control. There was no significant difference in muscle, brain, spleen, and liver uptakes between groups. Atomoxetine increased [¹⁸ F]FDG SUV of IBAT 1.7-fold greater than that in placebo-treated mice. There were no significant differences in all other organs compared to placebo-treated mice except liver (1.6 fold increase). A positive correlation between SUV levels of IBAT and CT Hounsfield unit (HU) (R² = 0.55, p < 0.001) and between CT HU levels of IBAT and liver (R² = 0.69, p < 0.006) was observed.ConclusionsThe three pharmacologic approaches reported here enhanced BAT metabolism by targeting different sites in adrenergic system as measured by [¹⁸ F]FDG PET/CT.     

Optimized Bayes variational regularization prior for 3D PET images

A new prior for variational Maximum a Posteriori regularization is proposed to be used in a 3D One-Step-Late (OSL) reconstruction algorithm accounting also for the Point Spread Function (PSF) of the PET system.The new regularization prior strongly smoothes background regions, while preserving transitions. A detectability index is proposed to optimize the prior.The new algorithm has been compared with different reconstruction algorithms such as 3D-OSEM + PSF, 3D-OSEM + PSF + post-filtering and 3D-OSL with a Gauss-Total Variation (GTV) prior.The proposed regularization allows controlling noise, while maintaining good signal recovery; compared to the other algorithms it demonstrates a very good compromise between an improved quantitation and good image quality.     

Usefulness of a breath-holding acquisition method in PET/CT for pulmonary lesions

Objective  To evaluate the usefulness of a breath-holding (BH) ¹⁸F-2-fluoro-2-deoxy-D-glucose positron emission tomography (¹⁸F-FDG-PET) technique for PET/computed tomography (CT) scanning of pulmonary lesions near the diaphragm, where image quality is influenced by respiratory motion. Methods  In a basic study, simulated breath-holding PET (sBH-PET) data were acquired by repeating image acquisition eight times with fixation of a phantom at 15 s/bed. Free-breathing PET (FB-PET) was simulated by acquiring data even as moving the phantom at 120 s/bed (sFB-PET). Images with total acquisition times of 15 s, 30 s, 45 s, 60 s, and 120 s were generated for sBHPET. Receiver-operating characteristic (ROC) analyses and determination of the statistical significance of differences between sFB-PET images and sBH-PET images were performed. A total of 22 pulmonary lesions in 21 patients (12 men and 9 women, mean age 61.3 ± 10.6 years, 10 benign lesions in 9 patients and 12 malignant lesions in 12 patients) were examined by FB-PET and BH-PET). For evaluation of these two acquisition methods, displacement of the lesion between CT and PET was considered to be a translation, and the statistical significance of differences in maximum standardized uptake value (SUV_max) of the lesion was assessed using the paired t test. Results  In the basic study, sBH-PET images with acquisition times of 45 s, 60 s, and 120 s had significantly higher diagnostic accuracy than 120-s sFB-PET images (P < 0.05). In clinical cases, translation of the BH-PET images was significantly lower than that of the FB-PET images (benign: 5.29 ± 4.02 mm vs. 11.79 ± 8.27 mm, P = 0.005; malignant: 4.29 ± 3.36 mm vs. 18.26 ± 12.31 mm, P = 0.003). The SUV_max of the lesions in the BH-PET images was significantly higher than that in the FB-PET images (benign: 2.40 ± 0.86 vs. 2.20 ± 0.85, P = 0.005; malignant: 4.84 ± 2.16 vs. 3.75 ± 2.11, P = 0.001). Conclusions  BH-PET provides images with better diagnostic accuracy, avoids image degradation owing to respiratory motion, and yields more accurate attenuation correction. This method is very useful for overcoming the problem of respiratory motion.