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Background: PSMA-PET is increasingly used for staging prostate cancer (PCA) patients. However, it is not clear if quantitative imaging parameters of positron emission tomography (PET) have an impact on disease progression and are thus important for the prognosis of localized PCA., Methods: This is a monocenter retrospective analysis of 86 consecutive patients with localized intermediate or high-risk PCA and PSMA-PET before treatment The quantitative PET parameters maximum standardized uptake value (SUV max ), tumor asphericity (ASP), PSMA tumor volume (PSMA-TV), and PSMA total lesion uptake (PSMA-TLU = PSMA-TV × SUV mean ) were assessed for their prognostic significance in patients with radiotherapy or surgery. Cox regression analyses were performed for biochemical recurrence-free survival, overall survival (OS), local control, and loco-regional control (LRC)., Results: 67% of patients had high-risk disease, 51 patients were treated with radiotherapy, and 35 with surgery. Analysis of metric PET parameters in the whole cohort revealed a significant association of PSMA-TV (p = 0.003), PSMA-TLU (p = 0.004), and ASP (p < 0.001) with OS. Upon binarization of PET parameters, several other parameters showed a significant association with clinical outcome. When analyzing high-risk patients according to the primary treatment approach, a previously published cut-off for SUV max (8.6) showed a significant association with LRC in surgically treated (p = 0.048), but not in primary irradiated (p = 0.34) patients. In addition, PSMA-TLU (p = 0.016) seemed to be a very promising biomarker to stratify surgical patients., Conclusion: Our data confirm one previous publication on the prognostic impact of SUV max in surgically treated patients with high-risk PCA. Our exploratory analysis indicates that PSMA-TLU might be even better suited. The missing association with primary irradiated patients needs prospective validation with a larger sample size to conclude a predictive potential. Trial registration Due to the retrospective nature of this research, no registration was carried out., (© 2024. The Author(s).)

Purpose: 68 Ga-labeled fibroblast activation protein inhibitor (FAPI) is a novel PET tracer with great potential for staging pancreatic cancer. Data on locally advanced or recurrent disease is sparse, especially on tracer uptake before and after high dose chemoradiotherapy (CRT). The aim of this study was to evaluate [ 68 Ga]Ga-FAPI-46 PET/CT staging in this setting. Methods: Twenty-seven patients with locally recurrent or locally advanced pancreatic adenocarcinoma (LRPAC n = 15, LAPAC n = 12) in stable disease or partial remission after chemotherapy underwent FAPI PET/CT and received consolidation CRT in stage M0 with follow-up FAPI PET/CT every three months until systemic progression. Quantitative PET parameters SUV max , SUV mean , FAPI-derived tumor volume and total lesion FAPI-uptake were measured in baseline and follow-up PET/CT scans. Contrast-enhanced CT (ceCT) and PET/CT data were evaluated blinded and staged according to TNM classification. Results: FAPI PET/CT modified staging compared to ceCT alone in 23 of 27 patients in baseline, resulting in major treatment alterations in 52% of all patients (30%: target volume adjustment due to N downstaging, 15%: switch to palliative systemic chemotherapy only due to diffuse metastases, 7%: abortion of radiotherapy due to other reasons). Regarding follow-up scans, major treatment alterations after performing FAPI PET/CT were noted in eleven of 24 follow-up scans (46%) with switch to systemic chemotherapy or best supportive care due to M upstaging and ablative radiotherapy of distant lymph node and oligometastasis. Unexpectedly, in more than 90 % of the follow-up scans, radiotherapy did not induce local fibrosis related FAPI uptake. During the first follow-up, all quantitative PET metrics decreased, and irradiated lesions showed significantly lower FAPI uptake in locally controlled disease (SUV max p = 0.047, SUV mean p = 0.0092) compared to local failure. Conclusion: Compared to ceCT, FAPI PET/CT led to major therapeutic alterations in patients with LRPAC and LAPAC prior to and after radiotherapy, which might help identify patients benefiting from adjustments in every treatment stage. FAPI PET/CT should be considered a useful diagnostic tool in LRPAC or LAPAC before and after CRT., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: PSMA PET is frequently used for staging of prostate cancer patients. Furthermore, there is increasing interest to use PET information for personalized local treatment approaches in surgery and radiotherapy, especially for focal treatment strategies. However, it is not well established which quantitative imaging parameters show highest correlation with clinical and histological tumor aggressiveness., Methods: This is a retrospective analysis of 135 consecutive patients with non-metastatic prostate cancer and PSMA PET before any treatment. Clinical risk parameters (PSA values, Gleason score and D'Amico risk group) were correlated with quantitative PET parameters maximum standardized uptake value (SUV max ), mean SUV (SUV mean ), tumor asphericity (ASP) and PSMA tumor volume (PSMA-TV)., Results: Most of the investigated imaging parameters were highly correlated with each other (correlation coefficients between 0.20 and 0.95). A low to moderate, however significant, correlation of imaging parameters with PSA values (0.19 to 0.45) and with Gleason scores (0.17 to 0.31) was observed for all parameters except ASP which did not show a significant correlation with Gleason score. Receiver operating characteristics for the detection of D'Amico high-risk patients showed poor to fair sensitivity and specificity for all investigated quantitative PSMA PET parameters (Areas under the curve (AUC) between 0.63 and 0.73). Comparison of AUC between quantitative PET parameters by DeLong test showed significant superiority of SUV max compared to SUV mean for the detection of high-risk patients. None of the investigated imaging parameters significantly outperformed SUV max ., Conclusion: Our data confirm prior publications with lower number of patients that reported moderate correlations of PSMA PET parameters with clinical risk factors. With the important limitation that Gleason scores were only biopsy-derived in this study, there is no indication that the investigated additional parameters deliver superior information compared to SUV max ., Competing Interests: HA declares research grants, travel grants, and lecture fees from Sirtex Medical Europe; HA confirms that none of the above funding sources were involved in the preparation of this paper. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zschaeck, Andela, Amthauer, Furth, Rogasch, Beck, Hofheinz and Huang.)

Background: Bayesian penalized likelihood reconstruction for PET (e.g., GE Q.Clear) aims at improving convergence of lesion activity while ensuring sufficient signal-to-noise ratio (SNR). This study evaluated reconstructed spatial resolution, maximum/peak contrast recovery (CRmax/CRpeak) and SNR of Q.Clear compared to time-of-flight (TOF) OSEM with and without point spread function (PSF) modeling., Methods: The NEMA IEC Body phantom was scanned five times (3 min scan duration, 30 min between scans, background, 1.5-3.9 kBq/ml F18) with a GE Discovery MI PET/CT (3-ring detector) with spheres filled with 8-, 4-, or 2-fold the background activity concentration (SBR 8:1, 4:1, 2:1). Reconstruction included Q.Clear (beta, 150/300/450), "PSF+TOF 4/16 " (iterations, 4; subsets, 16; in-plane filter, 2.0 mm), "OSEM+TOF 4/16 " (identical parameters), "PSF+TOF 2/17 " (2 it, 17 ss, 2.0 mm filter), "OSEM+TOF 2/17 " (identical), "PSF+TOF 4/8 " (4 it, 8 ss, 6.4 mm), and "OSEM+TOF 2/8 " (2 it, 8 ss, 6.4 mm). Spatial resolution was derived from 3D sphere activity profiles. RC as (sphere activity concentration [AC]/true AC). SNR as (background mean AC/background AC standard deviation)., Results: Spatial resolution of Q.Clear 150 was significantly better than all conventional algorithms at SBR 8:1 and 4:1 (Wilcoxon, each p < 0.05). At SBR 4:1 and 2:1, the spatial resolution of Q.Clear 300/450 was similar or inferior to PSF+TOF 4/16 and OSEM+TOF 4/16 . Small sphere CRpeak generally underestimated true AC, and it was similar for Q.Clear 150/300/450 as with PSF+TOF 4/16 or PSF+TOF 2/17 (i.e., relative differences < 10%). Q.Clear provided similar or higher CRpeak as OSEM+TOF 4/16 and OSEM+TOF 2/17 resulting in a consistently better tradeoff between CRpeak and SNR with Q.Clear. Compared to PSF+TOF 4/8 /OSEM+TOF 2/8 , Q.Clear 150/300/450 showed lower SNR but higher CRpeak., Conclusions: Q.Clear consistently improved reconstructed spatial resolution at high and medium SBR compared to PSF+TOF and OSEM+TOF, but only with beta = 150. However, this is at the cost of inferior SNR with Q.Clear 150 compared to Q.Clear 300/450 and PSF+TOF 4/16 /PSF+TOF 2/17 while CRpeak for the small spheres did not improve considerably. This suggests that Q.Clear 300/450 may be advantageous for the 3-ring detector configuration because the tradeoff between CR and SNR with Q.Clear 300/450 was superior to PSF+TOF 4/16 , OSEM+TOF 4/16 , and OSEM+TOF 2/17 . However, it requires validation by systematic evaluation in patients at different activity and acquisition protocols.

Purpose: To evaluate the accuracy of clinical parameters and established pre-treatment risk stratification systems for prostate cancer (PCa) in predicting PSMA-positive metastases in men undergoing Ga-68-PSMA PET/CT as initial staging examination., Materials and Methods: A retrospective analysis in 108 consecutive treatment-naïve patients with biopsy-proven PCa undergoing Ga-68-PSMA PET/CT (median age, 72 years [range, 49-82 years]) was performed. Prediction of PSMA-positive metastases by serum PSA, clinical T stage (cT), ISUP group, percentage of positive biopsy cores, and derived risk scores (D'Amico risk classification system, Roach [RF], Yale formula [YF], and Briganti nomogram [BN]) was examined with ROC analysis., Results: Any PSMA-positive metastases were found in 36 of 108 patients, including LN metastases in 28 patients, extrapelvic LN metastases in 15 patients, and organ metastases in 19 patients (bone, 19; lung, 1). AUCs for PSA, cT, ISUP, and percentage of positive biopsy cores regarding PSMA-positive metastases did not differ significantly (range, 0.6-0.8; each P > 0.05). D'Amico (AUC, 0.61-0.64) was inferior to RF (0.76-0.83), YF (0.81-0.86), and BN (0.73 to 0.88; each P < 0.05). Among the 89 high-risk patients (D'Amico), decision for or against PET imaging based on RF (cut-off, >18.0), YF (>10.8), or BN (>8.0) would have prevented PSMA PET/CT in 4 (5%), 15 (17%), or 18 patients (20%), respectively, while preserving a sensitivity ≥95% for PSMA-positive metastases., Conclusions: Clinical parameters and established risk stratification systems for PCa can predict Ga-68-PSMA PET-positive metastases in treatment-naïve patients. Especially YF and BN may improve identification of patients with the highest probability of metastatic disease detected by Ga-68-PSMA PET/CT., (© 2018 Wiley Periodicals, Inc.)

Aim: After detection of obstructive uropathy (OU), the indication for or against surgery is primarily based on the differential renal function (DRF). This is to compare functional magnetic resonance urography (fMRU) with dynamic renal scintigraphy (DRS) to assess OU and DRF in infants and children., Patients, Methods: Retrospective analysis in 30 patients (female: 16; male: 14; median age: 5.5 years [0.2-16.5]), divided into subgroup A (age: 0-2 years; n = 16) and B (> 2-17 years; n = 14). fMRU was assessed by measuring renal transit time (RTT) and volumetric DRF with CHOP fMRU tool (CT) and ImageJ MRU plug-in (IJ). OU detection by fMRU was compared with DRS (standard of reference) using areas under the curves (AUC) in ROC analyses. Concordant DRF was assumed if absolute deviation between fMRU and DRS was ≤ 5 %., Results: DRS confirmed fixed OU in 4/31 kidneys (12.9 %) in subgroup A. AUC of CT was 0.94 compared with 0.93 by IJ. Subgroup B showed fixed OU in 1/21 kidneys (4.8 %) with AUCs of 0.98 each. RTT measured neither by CT nor by IJ in confirmed fixed OU was < 1200 s - resulting in negative predictive values of 1.0 each. In subgroup A, DRF was concordant in 81.3 % of the kidneys for CT and DRS compared with 75.0 % for IJ and DRS. In subgroup B, CT and DRS were concordant in 91.7 %, and IJ and DRS in 45.8 % of the kidneys., Conclusion: fMRU accurately excluded fixed OU in infants and children, independent from the software used for quantification. However, assessment of DRF with fMRU deviated from DRS especially in infants who may profit most from early intervention. Thus, fMRU cannot fully replace DRS as primary functional examination. If, for clinical reasons, fMRU is performed in first place and it cannot exclude fixed OU, it should be followed by DRS for validation and DRF quantification.

Objectives: Routine visual assessment of positron emission tomography (PET) for thoracic lymph node (LN) staging in patients with non-small cell lung cancer (NSCLC) is limited by a lack of reliable assessment criteria. This study evaluates the accuracy and inter-rater agreement of a standardized approach with unified windowing and a PET-based visual score., Materials and Methods: This retrospective analysis included pretherapeutic FDG-PET data of 86 patients with NSCLC. After standardized windowing (threshold: 2×liver SUVmean) the LN uptake was assessed visually by three independent readers with varying levels of experience using a 4-step score (1, LN uptake≤mediastinal blood pool structures (MBPS); 2, MBPS3). The inexperienced (n=1), advanced (n=1), and expert readers (n=1) achieved similar accuracies of 93.5%, 91.4% and 92.1%, respectively (P>0.05 each). Cohen's κ ranged from 0.92 to 0.96 and Fleiss' κ was 0.93. ROC-analyses showed no significant differences between attendant readers within any subgroup (AUC, 0.92-0.96)., Conclusion: Applying unified windowing, the introduced PET-score achieved highly accurate and robust LN assessment. This approach may shorten learning curves of inexperienced readers, facilitate multicenter trials, and improve comparability of future studies., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To analyze the diagnostic performance of dual time point imaging (DTPI) for pre-therapeutic lymph node (LN) staging in non-small cell lung cancer (NSCLC)., Methods: This was a retrospective analysis of 47 patients with NSCLC who had undergone DTPI by PET (early + delayed) using F18-fluorodeoxyglucose (FDG). PET raw data were reconstructed iteratively (point spread function + time-of-flight). LN uptake in PET was assessed visually (four-step score) and semi-quantitatively (SUVmax, SUVmean, ratios LN/primary, LN/liver, and LN/mediastinal blood pool). DTPI analyses included retention indices (RIs), Δ-ratios and changes in visual score. Histology or cytology served as standards of reference. Accuracy was determined based on ROC analyses., Results: Thirty-six of 155 LNs were malignant. DTPI accuracy was low for all measures (visual assessment, 24.5%; RI SUVmax, 68.4%; RI SUVmean, 65.8%; Δ-ratios, 63.9-76.1%) and significantly inferior to early PET. Accuracies of early (range, 86.5-92.9%) and delayed PET (range, 85.2-92.9%) were comparable. At early PET, accuracy of the visual score (92.9%) was similar or superior to semi-quantitative analyses (range, 86.5-92.3%)., Conclusions: Using a modern PET/CT device and novel image reconstruction, neither additional delayed PET nor DTPI analyses improved the accuracy of PET-based LN staging. Dedicated visual assessment criteria performed very well., Key Points: • DTPI did not improve accuracy of PET-based LN staging in NSCLC. • Analyzed SUV ratios were not superior to LN SUVmax or SUVmean. • A four-step visual score may allow highly accurate, standardized LN assessment.

Background: The maximum standardized uptake value (SUVmax) is a common clinical parameter for quantification in F18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), but it is influenced by image reconstruction. The aim of this study was to analyze the association of SUVmax deviations related to point spread function (PSF) and time-of-flight (TOF) reconstruction with tumor-to-background ratios (TBR) in colorectal liver metastases (CRLM)., Methods: Fifteen patients (f, 6; m, 9; median age, 59 years; range, 32 to 72 years) with 28 liver metastases were included retrospectively. FDG-PET/CT imaging (median activity, 237 MBq; range, 231 to 252 MBq; median uptake, 61 min; range, 55 to 67 min) was performed on a Siemens Biograph mCT 64 followed by image reconstruction using 3D-ordered subset expectation maximization (3D-OSEM) or 3D-OSEM with PSF modeling - both with and without TOF information. Differences in SUVmax were analyzed using the Friedman test and Wilcoxon test for paired non-parametric data. The correlation of inter-method differences with the lesions' TBR was studied using Spearman's rank correlation coefficient (rho). Differences between lesions with low (<4.8) and high (>4.8) TBR were analyzed using the Mann-Whitney U test (TBR measured with 3D-OSEM; binarized by its median)., Results: There was a significant correlation of the lesions' TBR with relative SUVmax differences related to PSF (PSF + TOF vs. 3D-OSEM + TOF, rho = 0.61; PSF vs. 3D-OSEM, rho = 0.52) or TOF (PSF + TOF vs. PSF, rho = -0.58; 3D-OSEM + TOF vs. 3D-OSEM, rho = -0.61). Accordingly, PSF algorithms only showed higher SUVmax than non-PSF algorithms in lesions with a high TBR (median differences at low/high TBR, +2.6%/+9.1% [PSF + TOF vs. 3D-OSEM + TOF]; +0.7%/+6.4% [PSF vs. 3D-OSEM]). TOF integration also led to higher SUVmax but mainly at low TBR (low/high TBR, +10.4%/+1.8% [PSF + TOF vs. PSF]; +8.6%/-0.1% [3D-OSEM + TOF vs. 3D-OSEM])., Conclusions: Both PSF and TOF reconstruction resulted in a substantial alteration of SUVmax in CRLM. TOF provided the highest SUVmax increase in low-contrast lesions while - vice versa - PSF showed the most relevant increase in high-contrast lesions. Thus, one should be aware that quantitative analyses of lesions with varying TBR, e.g., in radiotherapy or follow-up studies, may be mainly affected by either PSF or TOF reconstruction, respectively.

Background: F18-fluorodeoxyglucose positron-emission tomography (FDG-PET) reconstruction algorithms can have substantial influence on quantitative image data used, e.g., for therapy planning or monitoring in oncology. We analyzed radial activity concentration profiles of differently reconstructed FDG-PET images to determine the influence of varying signal-to-background ratios (SBRs) on the respective spatial resolution, activity concentration distribution, and quantification (standardized uptake value [SUV], metabolic tumor volume [MTV])., Methods: Measurements were performed on a Siemens Biograph mCT 64 using a cylindrical phantom containing four spheres (diameter, 30 to 70 mm) filled with F18-FDG applying three SBRs (SBR1, 16:1; SBR2, 6:1; SBR3, 2:1). Images were reconstructed employing six algorithms (filtered backprojection [FBP], FBP + time-of-flight analysis [FBP + TOF], 3D-ordered subset expectation maximization [3D-OSEM], 3D-OSEM + TOF, point spread function [PSF], PSF + TOF). Spatial resolution was determined by fitting the convolution of the object geometry with a Gaussian point spread function to radial activity concentration profiles. MTV delineation was performed using fixed thresholds and semiautomatic background-adapted thresholding (ROVER, ABX, Radeberg, Germany)., Results: The pairwise Wilcoxon test revealed significantly higher spatial resolutions for PSF + TOF (up to 4.0 mm) compared to PSF, FBP, FBP + TOF, 3D-OSEM, and 3D-OSEM + TOF at all SBRs (each P < 0.05) with the highest differences for SBR1 decreasing to the lowest for SBR3. Edge elevations in radial activity profiles (Gibbs artifacts) were highest for PSF and PSF + TOF declining with decreasing SBR (PSF + TOF largest sphere; SBR1, 6.3%; SBR3, 2.7%). These artifacts induce substantial SUVmax overestimation compared to the reference SUV for PSF algorithms at SBR1 and SBR2 leading to substantial MTV underestimation in threshold-based segmentation. In contrast, both PSF algorithms provided the lowest deviation of SUVmean from reference SUV at SBR1 and SBR2., Conclusions: At high contrast, the PSF algorithms provided the highest spatial resolution and lowest SUVmean deviation from the reference SUV. In contrast, both algorithms showed the highest deviations in SUVmax and threshold-based MTV definition. At low contrast, all investigated reconstruction algorithms performed approximately equally. The use of PSF algorithms for quantitative PET data, e.g., for target volume definition or in serial PET studies, should be performed with caution - especially if comparing SUV of lesions with high and low contrasts.

Background: While non-rigid fusion is by definition expected to alter the information of positron emission tomography (PET) data, we assessed whether rigid transformation also influences metabolic tumor volume (MTV) determination., Methods: The PET/computed tomography (CT) data of 28 solid pulmonary lesions of 20 tumor patients examined with 18 F-Fluordeoxyglucose (FDG) was retrospectively analyzed. The original (OR) hardware-coregistered PET images were fused with contrast-enhanced diagnostic CT (CT1, 1 mm slices) and low dose CT (CT5, 5 mm slices). After automatic rigid transformation (Mirada Fusion7D) using two algorithms (rigid fast (RF), rigid slow (RS)), MTV and maximal standardized uptake value (SUVmax) were determined applying four different segmentation methods with either fixed or background-adapted thresholding and compared to OR-PET data., Results: Relative differences in SUVmax compared to OR data revealed no significant differences for RF (median, -0.1%; interquartile range (IQR), -1.1% to 0.9%; p = 0.75) and RS (median, 0.5%; IQR, -0.6% to 1.3%; p = 0.19) in CT1, whereas in CT5 significant deviations were observed for RF (median, -9.0%; IQR, -10.9 to -6.1; p < 0.001) and RS (median, -8.4%; IQR, -11.1 to -5.6; p < 0.001). Relative MTV differences were 0.7% (IQR, -3.0% to 2.7%; p = 0.76) for RF and -1.3% (IQR, -3.6% to 0.9%; p = 0.12) for RS in CT1. Coregistration led to significant MTV differences in RF (median, 10.4%; IQR, 7.4% to 16.7%; p < 0.001) and RS (median, 10.6%; IQR, 5.4% to 17.7%; p < 0.001) in CT5., Conclusions: Rigid coregistration of PET data allows a quantitative evaluation with reasonable accuracy in most cases. However, in some cases, it can result in substantial deviations of MTV and SUVmax. Therefore, it is recommended to perform quantitative evaluation in the original PET data rather than in coregistered PET data.