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Recently introduced long-axial field-of-view (LAFOV) PET/CT systems represent one of the most significant advancements in nuclear medicine since the advent of multi-modality PET/CT imaging. The higher sensitivity exhibited by such systems allow for reductions in applied activity and short duration scans. However, we consider this to be just one small part of the story: Instead, the ability to image the body in its entirety in a single FOV affords insights which standard FOV systems cannot provide. For example, we now have the ability to capture a wider dynamic range of a tracer by imaging it over multiple half-lives without detrimental image noise, to leverage lower radiopharmaceutical doses by using dual-tracer techniques and with improved quantification. The potential for quantitative dynamic whole-body imaging using abbreviated protocols potentially makes these techniques viable for routine clinical use, transforming PET-reporting from a subjective analysis of semi-quantitative maps of radiopharmaceutical uptake at a single time-point to an accurate and quantitative, non-invasive tool to determine human function and physiology and to explore organ interactions and to perform whole-body systems analysis. This article will share the insights obtained from 2 years’ of clinical operation of the first Biograph Vision Quadra (Siemens Healthineers) LAFOV system. It will also survey the current state-of-the-art in PET technology. Several technologies are poised to furnish systems with even greater sensitivity and resolution than current systems, potentially with orders of magnitude higher sensitivity. Current barriers which remain to be surmounted, such as data pipelines, patient throughput and the hindrances to implementing kinetic analysis for routine patient care will also be discussed.

Background: Accurate kinetic modelling of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) data requires accurate knowledge of the available tracer concentration in the plasma during the scan time, known as the arterial input function (AIF). The gold standard method to derive the AIF requires collection of serial arterial blood samples but the introduction of long axial field of view (LAFOV) PET systems enables use of non-invasive image derived input functions (IDIF) from large blood pools such as the aorta without any need for bed movement. However, such protocols require a prolonged dynamic PET acquisition which is impractical in a busy clinical setting. Population-based input functions (PBIF) have previously shown potential in accurate Patlak analysis of 18F-FDG datasets and can enable the use of shortened dynamic imaging protocols. We not exploit the high sensitivity and temporal resolution of a LAFOV PET system and explore use of PBIF with abbreviated protocols in 18F-FDG total body kinetic modelling. Methods: Dynamic PET data were acquired in 24 oncological subjects for 65 minutes following the administration of 18F-FDG. IDIFs were extracted from the descending thoracic aorta and a PBIF was generated from 16 datasets. Five different scaled PBIFs (sPBIF) were generated by scaling the PBIF with AUC of IDIF curve tails using various portions of image data (35-65, 40-65, 45-65, 50-65 and 55-65 min post injection). The sPBIFs were compared with the IDIFs using the AUCs and Patlak Ki estimates in tumour lesions and cerebral grey matter. Patlak plot start time (t*) was also varied to evaluate the performance of shorter acquisitions on accuracy of Patlak Ki estimates. Patlak Ki estimates with IDIF and t*=35 min was used as reference and mean bias and precision (standard deviation of bias) were calculated to assess relative performance of different sPBIFs. Comparison of parametric images generated using IDIF and sPBIFs was also performed. Results: There was no statistically significant difference between AUCs of the IDIF and sPBIFs (Wilcoxon test: P>0.05). The sPBIF55-65 showed the best performance with 1.5% bias and %6.8 precision in tumour lesions. Using the sPBIF55-65 with Patlak model, 20 minutes of PET data (i.e. 45 to 65 min post injection) achieved i estimates in tumour lesions compared to the estimates with the IDIF. Parametric images reconstructed using the IDIF and sPBIFs with and without an abbreviated protocol were visually comparable. Using Patlak Ki generated with an IDIF and 30 mins of PET data as reference, Patlak Ki images generated using sPBIF55-65 with 20 minutes of PET data (t*=45 min) provided excellent image quality with structural similarity index measure > 0.99 and peak signal-to-noise ratio > 55 dB. Conclusion: We demonstrate the feasibility of performing accurate 18F-FDG Patlak analysis using sPBIFs with only 20 minutes of PET data from a LAFOV PET scanner.

It is still debating if individualized dose should be applied for the emerging PSMA-targeted radionuclide therapy (RLT). A critical consideration in this debate is the necessity and feasibility of individual estimation of post-therapy dosimetry before the treatment. In this study, we aimed to prove the concept of individual dosimetry prediction based on pre-therapy imaging and laboratory measurements. Methods: 23 patients with metastatic castration-resistant prostate cancer (mCRPC) treated with 177Lu-PSMA-I&T RLT were included retrospectively. Included patients had available pre-therapeutic 68Ga-PSMA-HEBD-CC PET/CT and at least 3 planar and 1 SPECT/CT dosimetry imaging. Overall, 43 cycles of 177Lu-PSMA I&T RLT were applied. Organ-based standard uptake value (SUV) uptake was obtained from pretherapy PET/CT scans. Patient individual dosimetry was calculated for kidney, liver, spleen, and salivary glands using Hermes Hybrid Dosimetry 4.0 from the post-treatment 177Lu-PSMA I&T imaging studies. Machine learning methods were explored for individual dose prediction from PET images. The accuracy of these dose predictions was compared with the accuracy of population-based dosimetry estimates. Mean absolute percentage error was used to assess the prediction error of estimated dosimetry. Results: An optimal machine learning method achieved a dosimetry prediction error of 15.8 ± 13.2% for kidney, 29.6%±13.7% for liver, 23.8%±13.1% for salivary glands and 32.1 ± 31.4% for spleen. In contrast, the prediction based on literature population mean has significantly larger error (p Conclusion: The preliminary results confirmed the feasibility of individual estimation of post-therapy dosimetry before the RLT and its added value to empirical population-based estimation. The exploration of individual dose prediction may support the identification of the role of treatment planning for RLT.

Background Our aim was to determine sets of reconstruction parameters for the Biograph Vision Quadra (Siemens Healthineers) PET/CT system that result in quantitative images compliant with the European Association of Nuclear Medicine Research Ltd. (EARL) criteria. Using the Biograph Vision 600 (Siemens Healthineers) PET/CT technology but extending the axial field of view to 106 cm, gives the Vision Quadra currently an around fivefold higher sensitivity over the Vision 600 with otherwise comparable spatial resolution. Therefore, we also investigated how the number of incident positron decays—i.e., exposure—affects EARL compliance. This will allow estimating a minimal acquisition time or a minimal applied dose in clinical scans while retaining data comparability. Methods We measured activity recovery curves on a NEMA IEC body phantom filled with an aqueous 18F solution and a sphere to background ratio of 10–1 according to the latest EARL guidelines. Reconstructing 3570 image sets with varying OSEM PSF iterations, post-reconstruction Gaussian filter full width at half maximum (FWHM), and varying exposure from 59 kDecays/ml (= 3 s frame duration) to 59.2 MDecays/ml (= 1 h), allowed us to determine sets of parameters to achieve compliance with the current EARL 1 and EARL 2 standards. Recovery coefficients (RCs) were calculated for the metrics RCmax, RCmean, and RCpeak, and the respective recovery curves were analyzed for monotonicity. The background’s coefficient of variation (COV) was also calculated. Results Using 6 iterations, 5 subsets and 7.8 mm Gauss filtering resulted in optimal EARL1 compliance and recovery curve monotonicity in all analyzed frames, except in the 3 s frames. Most robust EARL2 compliance and monotonicity were achieved with 2 iterations, 5 subsets, and 3.6 mm Gauss FWHM in frames with durations between 30 s and 10 min. RCpeak only impeded EARL2 compliance in the 10 s and 3 s frames. Conclusions While EARL1 compliance was robust over most exposure ranges, EARL2 compliance required exposures between 1.2 MDecays/ml to 11.5 MDecays/ml. The Biograph Vision Quadra’s high sensitivity makes frames as short as 10 s feasible for comparable quantitative images. Lowering EARL2 RCmax limits closer to unity would possibly even permit shorter frames.

ZusammenfassungDas Prostatakarzinom (PCa) ist der weltweit häufigste maligne Tumor bei Männern. Seit ihrer klinischen Einführung im Jahr 2011 hat sich sowohl die PET/CT als auch die Radioligandentherapie mit PSMA-Liganden zur Diagnostik bzw. Therapie des PCa weltweit rasch ausgebreitet. Obwohl die PSMA-PET/CT als ein signifikanter Durchbruch in der Diagnostik des PCa gilt, stellt die Evaluation und Kontrolle aller Tumorherde inklusive ihrer Volumina und Charakteristiken bei fortgeschrittenem, multimetastatischem PCa nach wie vor eine große Herausforderung dar. Diese gilt es zu bewältigen, um beispielsweise eine Optimierung der Endoradiotherapie mit PSMA-Liganden zu erreichen. In diesem Kontext könnte die künstliche Intelligenz, die in den letzten Jahren signifikante Fortschritte erzielt hat, in der nahen Zukunft eine wichtige Rolle spielen. Die Artificial Intelligence (AI) hat bereits demonstriert, dass sie den menschlichen Fähigkeiten zur Datenverarbeitung überlegen sein kann und bietet damit großes Potenzial zur Verbesserung der Detektion, Quantifizierung und Charakterisierung von PCa-Herden in der PSMA-PET/CT.Die hier vorliegende Schrift befasst sich mit den aktuellen Entwicklungen der künstlichen Intelligenz für den Einsatz in der PSMA-PET/CT und den sich daraus bietenden Möglichkeiten.

Purpose: Uncertain bone lesions (UBL) with intensive radiopharmaceutical avidity are frequently observed in patients undergoing [18F]PSMA-1007 PET/CT for the detection of prostate cancer (PC). Such lesions can pose diagnostic conundrums and risk an incorrect staging. The aim of this short communication is to share the results of PET-guided biopsies of such lesions. Methods: A retrospective analysis revealed 10 patients who were referred to our department for PET-guided biopsy of UBL visible in a previous [18F]PSMA-1007 PET/CT. [18F]-PSMA-1007 PET-guided biopsy was conducted for 11 PSMA-avid bone lesions in these 10 patients. The biopsy materials were analysed for tissue typing and immunohistochemistry (IHC) was performed for prostate-specific-membrane-antigen (PSMA) expression. The scans were analysed by two experienced physicians in a consensus read for clinical characteristics and radiopharmaceutical uptake of lesions. Results: 1/11 (9.1%) of the lesions biopsied was confirmed as bone metastasis of PC with intense PSMA-expression while 10/11 (90.9%) lesions were revealed to be unremarkable bone tissue without evidence of PSMA-expression at IHC. Amongst all bone lesions assessed by biopsy, eight were visually classified as being at high risk of malignancy in the PET/CT (SUVmean 12.0 ± 8.1; SUVmax 18.8 ± 13.1), three as equivocal (SUVmean 4.6 ± 2.1; SUVmax 7.2 ± 3.0) and zero as low risk. No UBL had any CT correlate. Conclusions: In this cohort biopsy revealed that a small but relevant number of UBL are true metastases. For those confirmed as benign, no PSMA-expression at IHC was observed, suggesting a non-PSMA mediated cause for intensive [18F]PSMA-1007-uptake of which the reason remains unclear. Readers must interpret such lesions with caution in order to reduce the risk of erroneous staging and subsequent treatment. PET-guided biopsy, particularly in the absence of morphological changes in the CT, can be a useful method to clarify such lesions.

Uncertain focal bone uptake (UBU) with intensive radiopharmaceutical avidity are frequently observed in patients undergoing [A retrospective analysis revealed 10 patients who were referred to our department for PET-guided biopsy of UBU visible in a previous [One out of 11 (9.1%) of the foci biopsied was confirmed as bone metastasis of PC with intense PSMA-expression, while 10/11 (90.9%) foci were revealed to be unremarkable bone tissue without evidence of PSMA expression at IHC. Amongst all bone foci assessed by biopsy, eight were visually classified as being at high risk of malignancy in the PET/CT (SUVmean 12.0 ± 8.1; SUVmax 18.8 ± 13.1), three as equivocal (SUVmean 4.6 ± 2.1; SUVmax 7.2 ± 3.0) and zero as low risk. No UBU had any CT correlate.This cohort biopsy revealed that a small but relevant number of UBU are true metastases. For those confirmed as benign, no PSMA expression at IHC was observed, suggesting a non-PSMA mediated cause for intensive [

Aim Despite increasing use for the detection of biochemically recurrent prostate cancer (rPC), the diagnostic accuracy of positron emission tomography/computed tomography (PET/CT) with [18F]PSMA-1007 remains only partially investigated. The aim of this study was to determine the sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) for PC-local recurrence and metastases on a per region basis. Materials and methods One hundred seventy-seven consecutive patients undergoing [18F]PSMA-1007 PET/CT for rPC were retrospectively analysed. Six body regions were defined: prostate fossa, pelvic lymph nodes (LN), retroperitoneal LN, supradiaphragmatic LN, bones, and soft tissue. A region was counted positive if at least one PSMA-positive lesion suspicious for PC was observed. Confirmation of a true-positive PSMA-avid lesion was defined as positive by histopathology, fall in serum prostate-specific antigen (PSA) (> 50%) after targeted therapy or confirmatory further CT, MRI, PET/CT, or bone scan imaging. Regions where additional imaging was able to confirm the absence of suspicious PC lesions or regions outside exclusively targeted RT with serum PSA decline (> 50%) were counted as true-negative regions. SE, SP, PPV, and NPV were calculated for all six regions. Results The overall PET-positivity rate was 91%. Conclusive follow-up for affirmation or refutation of a PSMA-positive lesion was available for 81/152 patients on a per region basis. In this subgroup, overall sensitivity, specificity, PPV, and NPV were 95% (CI: 0.90–0.98), 89% (CI: 0.83–0.93), 86% (0.80–0.90), and 96% (CI: 0.92–0.98), respectively. On a per region basis, PPV was 97% (CI: 0.83–0.99) for local recurrence, 93% (CI: 0.78–0.98) for pelvic LN, 87% (CI: 0.62–0.96) for retroperitoneal LN, 82% (CI: 0.52–0.95) for supradiaphragmatic LN, and 79% (0.65–0.89) for bone lesions. The number of solid organ metastases (n = 6) was too small for an accurate statistical analysis. Conclusion The known high PET-positivity rate of [18F]PSMA-1007 PET/CT in rPC was confirmed, with corresponding high (> 90%) sensitivity and NPV on a per region basis. However, overall PPV was limited (86%), particularly for bone lesions (79%), which are a potential diagnostic weaknesses when using this tracer.

During disease progression from primary towards metastatic prostate cancer (PCa), and in particular bone metastases, the tumor microenvironment (TME) evolves in parallel with the cancer clones, altering extracellular matrix composition (ECM), vasculature architecture, and recruiting specialized tumor-supporting cells that favor tumor spread and colonization at distant sites. We introduce the clinical profile of advanced metastatic PCa in terms of common genetic alterations. Findings from recently developed models of PCa metastatic spread are discussed, focusing mainly on the role of the TME (mainly matrix and fibroblast cell types), at distinct stages: premetastatic niche orchestrated by the primary tumor towards the metastatic site and bone metastasis. We report evidence of premetastatic niche formation, such as the mechanisms of distant site conditioning by extracellular vesicles, chemokines and other tumor-derived mechanisms, including altered cancer cell-ECM interactions. Furthermore, evidence supporting the similarities of stroma alterations among the primary PCa and bone metastasis, and contribution of TME to androgen deprivation therapy resistance are also discussed. We summarize the available bone metastasis transgenic mouse models of PCa from a perspective of pro-metastatic TME alterations during disease progression and give an update on the current diagnostic and therapeutic radiological strategies for bone metastasis clinical management.

Purpose Although treatment planning and individualized dose application for emerging prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) are generally recommended, it is still difficult to implement in practice at the moment. In this study, we aimed to prove the concept of pretherapeutic prediction of dosimetry based on imaging and laboratory measurements before the RLT treatment. Methods Twenty-three patients with metastatic castration-resistant prostate cancer (mCRPC) treated with 177Lu-PSMA I&T RLT were included retrospectively. They had available pre-therapy 68 Ga-PSMA-HEBD-CC PET/CT and at least 3 planar and 1 SPECT/CT imaging for dosimetry. Overall, 43 cycles of 177Lu-PSMA I&T RLT were applied. Organ-based standard uptake values (SUVs) were obtained from pre-therapy PET/CT scans. Patient dosimetry was calculated for the kidney, liver, spleen, and salivary glands using Hermes Hybrid Dosimetry 4.0 from the planar and SPECT/CT images. Machine learning methods were explored for dose prediction from organ SUVs and laboratory measurements. The uncertainty of these dose predictions was compared with the population-based dosimetry estimates. Mean absolute percentage error (MAPE) was used to assess the prediction uncertainty of estimated dosimetry. Results An optimal machine learning method achieved a dosimetry prediction MAPE of 15.8 ± 13.2% for the kidney, 29.6% ± 13.7% for the liver, 23.8% ± 13.1% for the salivary glands, and 32.1 ± 31.4% for the spleen. In contrast, the prediction based on literature population mean has significantly larger MAPE (p Conclusion The preliminary results confirmed the feasibility of pretherapeutic estimation of treatment dosimetry and its added value to empirical population-based estimation. The exploration of dose prediction may support the implementation of treatment planning for RLT.

A Correction to this paper has been published: 10.1007/s00259-021-05300-8

Despite increasing use for the detection of biochemically recurrent prostate cancer (rPC), the diagnostic accuracy of positron emission tomography/computed tomography (PET/CT) with [One hundred seventy-seven consecutive patients undergoing [The overall PET-positivity rate was 91%. Conclusive follow-up for affirmation or refutation of a PSMA-positive lesion was available for 81/152 patients on a per region basis. In this subgroup, overall sensitivity, specificity, PPV, and NPV were 95% (CI: 0.90-0.98), 89% (CI: 0.83-0.93), 86% (0.80-0.90), and 96% (CI: 0.92-0.98), respectively. On a per region basis, PPV was 97% (CI: 0.83-0.99) for local recurrence, 93% (CI: 0.78-0.98) for pelvic LN, 87% (CI: 0.62-0.96) for retroperitoneal LN, 82% (CI: 0.52-0.95) for supradiaphragmatic LN, and 79% (0.65-0.89) for bone lesions. The number of solid organ metastases (n = 6) was too small for an accurate statistical analysis.The known high PET-positivity rate of [

To investigate the kinetics ofTwenty-four oncological patients underwent dynamicWe report estimates of kinetic parameters and metabolic rate of glucose consumption (MRWe performed pharmacokinetic modelling of multiple organs using linear and non-linear models using dynamic total-body

This study proposes an automated prostate cancer (PC) lesion characterization method based on the deep neural network to determine tumor burden on 68Ga-PSMA-11 PET/CT to potentially facilitate the optimization of PSMA-directed radionuclide therapy. We collected 68Ga-PSMA-11 PET/CT images from 193 patients with metastatic PC at three medical centers. For proof-of-concept, we focused on the detection of pelvis bone and lymph node lesions. A deep neural network (triple-combining 2.5D U-Net) was developed for the automated characterization of these lesions. The proposed method simultaneously extracts features from axial, coronal, and sagittal planes, which mimics the workflow of physicians and reduces computational and memory requirements. Among all the labeled lesions, the network achieved 99% precision, 99% recall, and an F1 score of 99% on bone lesion detection and 94%, precision 89% recall, and an F1 score of 92% on lymph node lesion detection. The segmentation accuracy is lower than the detection. The performance of the network was correlated with the amount of training data. We developed a deep neural network to characterize automatically the PC lesions on 68Ga-PSMA-11 PET/CT. The preliminary test within the pelvic area confirms the potential of deep learning methods. Increasing the amount of training data should further enhance the performance of the proposed method and may ultimately allow whole-body assessments.

PURPOSE Digital PET/CT scanners represent a significant step forward in molecular imaging. We report here the clinical impact of digital PET in PSMA-PET/CT. METHODS In this retrospective study, 88 consecutive patients who underwent [68Ga]Ga-PSMA-11 PET/CT on a digital PET/CT (dPET/CT) scanner for recurrent prostate cancer (PC) were included in a first cohort. In a second step, 88 individuals who underwent an analogue [68Ga]Ga-PSMA-11 PET/CT (aPET/CT) were selected after they were matched to the first cohort for clinical parameters. Following consensus read by two nuclear medicine physicians, the number and type of PC lesions as well as benign, PSMA-positive lesions were recorded. The results were complemented by extensive [68Ga]Ga phantom measurements to determine imaging characteristics of both scanners. RESULTS dPET/CT revealed a greater number of PC lesions compared to aPET/CT (326 versus 142) as well as a proportional increase in benign causes of tracer-uptake (144 versus 65). A greater number of scans were noted as pathological for PC on dPET/CT (74/88) compared to aPET/CT (64/88, p < 0.05). The PSMA positivity rate for PC was significantly higher in dPET/CT for the lowest PSA values (PSA < 2.0 ng/ml, p < 0.05). CONCLUSION dPET/CT detected more PC lesions compared to aPET/CT. A significantly higher rate of pathological PET/CTs was noted in the group with the lowest PSA values. A higher number of benign PSMA-positive lesions were also noted in dPET/CT. The differences could be plausibly explained by the measured imaging characteristics of the scanners.

Die Positronenemissionstomographie/Computertomographie (PET/CT) mit Liganden des Prostataspezifischen Membranantigens (PSMA) und die PSMA-Therapie haben sich seit ihrer klinischen Einfuhrung in 2011 weltweit rasant ausgebreitet. Aktuelle Erkenntnisse sowohl uber die PSMA-PET/CT als auch uber die PSMA-Therapie werden zusammengefasst. Erkenntnisse aus der Literatur und Erfahrungen der Autoren wurden zusammengetragen. Es zeigt sich eine sehr hohe Sensitivitat und Spezifitat der PSMA-PET/CT sowohl beim Rezidivprostatakarzinom (‑PC) als auch beim Primarstaging des PC mit mittlerem und hohem Risikoprofil. Die Ergebnisse der PSMA-Therapie als Drittlinientherapie bei Patienten mit metastasiertem, kastrationsresistentem PC sind vielversprechend. Die PSMA-PET/CT hat sich mittlerweile als Goldstandard in der Diagnostik des Rezidiv-PC etabliert und ist dabei, dieselbe Rolle auch beim Primarstaging des PC mit mittlerem und hohem Risikoprofil zu ubernehmen. Die PSMA-Therapie wird in einer stets wachsenden Zahl an Zentren als Drittlinientherapie bei metastasiertem, kastrationsresistentem PC routinemasig durchgefuhrt.

PURPOSE Dual-time point PET/CT scanning with [68Ga]Ga-PSMA-11 in the diagnosis of prostate cancer (PC) has been advanced as a method to increase detection of PC lesions, particularly at early stages of biochemical recurrence and as a potential means to aid the discrimination between benign and pathological prostate-specific membrane antigen (PSMA) uptake. However, the assumption that all PC lesions uniformly exhibit increasing tracer uptake at delayed imaging has not yet been investigated, which this present study aims to address. METHODS One hundred consecutive patients with biochemically recurrent PC who received standard and late [68Ga]Ga-PSMA-11 PET/CT (by local protocol at 1.5 h "standard" and 2.5 h p.i. "late") underwent retrospective evaluation. All lesions with a tracer uptake above local background were analysed with regard to their maximum standardised uptake values at standard and late images (SUVmax) and characterised according to their morphological characteristics. RESULTS Seventy-nine of 100 patients had PSMA-positive scans, in whom a total of 185 individual PSMA-positive lesions were identified. These were morphologically characterised as bone lesions (n = 48), solid organ lesions (n = 3), lymph node (LN) lesions (n = 78) and locally recurrent lesions in the prostatic fossa or seminal vesicles (n = 56). The relative uptake between standard and late imaging was considered; all lesions classified as local recurrence presented with increasing (86%) or stable patterns of tracer uptake (14%). In contrast, only 58% of bone lesions exhibited increasing tracer uptake, with 21% exhibiting a stable pattern and 21% exhibiting a decreasing tracer uptake at late imaging. CONCLUSION A heterogeneous pattern of dynamic tracer uptake was observed, with a largely increasing pattern observed for locally recurrent lesions and lymph nodes and a significant proportion of bone lesions exhibiting decreasing tracer uptake. The results are of significance not only in the imaging and identification of PC lesions, but they also have implications for PSMA-directed ligand therapy.

PURPOSE So far, there have been very few studies which provide a direct comparison between MRI and PSMA-ligand PET/CT for the detection of recurrent prostate cancer (rPC). This present study therefore aims to provide further clinical data in order to resolve this urgent clinical question, and thereby strengthen clinical recommendations. METHODS A retrospective analysis was performed for patients who were scanned at our institution with whole-body PSMA-PET/CT (tracer: 68Ga-PSMA-11) between January 2017 and September 2018 in order to detect rPC. Amongst them, 43 underwent an additional pelvic MRI within 2 months. Both modalities were compared as follows: a consensus read of the PET data was performed by two nuclear physicians. All lesions were recorded with respect to their type and localization. The same process was conducted by two radiologists for pelvic MRI. Thereafter, both modalities were directly compared for every patient and lesion. RESULTS Overall, 30/43 patients (69.8%) presented with a pathologic MRI and 38/43 (88.4%) with a pathologic PSMA-PET/CT of the pelvis. MRI detected 53 pelvic rPC lesions (13 of them classified as "uncertain") and PSMA-PET/CT detected 75 pelvic lesions (three classified as "uncertain"). The superiority of PSMA-PET/CT was statistically significant only if uncertain lesions were classified as false-positive. CONCLUSIONS PSMA-PET/CT detected more pelvic lesions characteristic for rPC when compared to MRI. In order to detect rPC, a potential future scenario could be conducting first a PSMA-PET/CT. Combining the advantages of both modalities in hybrid PET/MRI scanners would be an ideal future scenario.

ZusammenfassungDas Prostatakarzinom (PCa) ist der weltweit häufigste maligne Tumor bei Männern. Seit ihrer klinischen Einführung in 2011 hat sich sowohl die PET/CT als auch die Radioligandentherapie mit PSMA-Liganden zur Diagnostik bzw. Therapie des PCa weltweit rasch ausgebreitet. Obwohl die PSMA-PET/CT als ein signifikanter Durchbruch in der Diagnostik des PCa gilt, stellt die Evaluation und Kontrolle aller Tumorherde inklusive ihrer Volumina und Charakteristika bei fortgeschrittener, multimetastatischer PCa nach wie vor eine große Herausforderung dar. Diese gilt es zu bewältigen, um beispielsweise eine Optimierung der Endoradiotherapie mit PSMA-Liganden zu erreichen. In diesem Kontext könnte die künstliche Intelligenz, die in den letzten Jahren signifikante Fortschritte erzielt hat, in der nahen Zukunft eine wichtige Rolle spielen. Die Artificial Intelligence (AI) hat bereits demonstriert, dass sie den menschlichen Fähigkeiten zur Datenverarbeitung überlegen sein kann und bietet damit großes Potential zur Verbesserung der Detektion, Quantifizierung und Charakterisierung von PCa-Herden in der PSMA-PET/CT. Die hier vorliegende Schrift befasst sich mit den aktuellen Entwicklungen der künstlichen Intelligenz für den Einsatz in der PSMA-PET/CT und den sich daraus bietenden Möglichkeiten.

Prostate-specific membrane antigen-PET/computed tomography (PSMA-PET/CT) is the investigation of choice for imaging prostate cancer. Demonstrating high diagnostic accuracy, PSMA-PET/CT detects disease at very early stages of recurrence, where the chances of a definitive cure may be at their greatest. A number of PSMA-radioligands are in established clinical routine, and there are currently only limited data and no single tracer can clearly be advocated over the others at present. Further clinical trial data, comparing and contrasting radiotracers and reporting outcome-based data are necessary to further increase the implementation of this very promising imaging modality.

Prostate-specific membrane antigen (PSMA) has been the subject of numerous studies within the last 3 decades. PSMA-targeted imaging and therapy have significantly changed the management of patients with prostate cancer in various disease stages, especially in advanced metastasized castration-resistant prostate cancer. Lutetium-177-conjugated PSMA-617 or PSMA-IT (Lu-PSMA) has shown promising results in multicenter retrospective and monocenter prospective trials. The aim of this review is to provide an overview of the history and current and future developments of PSMA-targeted therapy. A special focus of this review is on PSMA PET-guided management of patients receiving PSMA-targeted radioligand therapy.

PSMA PET/CT is routinely used for the detection of prostate cancer (PC). However, increased PSMA-ligand uptake has been described in a variety of benign and malignant tissues. A 71-year-old man with biochemical recurrence of PC initially treated with radical prostatectomy was referred for PSMA-ligand PET/CT. Apart from 1 lymph node with intense PSMA-ligand uptake, suspicious for metastasis, disseminated PSMA-ligand-avid subcutaneous lesions were seen. Histopathology of 1 of these lesions revealed an epidermoid cyst. Physicians should remain cognizant of non-PC-related causes of increased PSMA-ligand uptake, of which this case represent yet another example.

To investigate the performance of the new long axial field-of-view (LAFOV) Biograph Vision Quadra PET/CT and a standard axial field-of-view (SAFOV) Biograph Vision 600 PET/CT (both: Siemens Healthineers) system using an intra-patient comparison.Forty-four patients undergoing routine oncological PET/CT were prospectively included and underwent a same-day dual-scanning protocol following a single administration of eitherEquivalent target lesion integral activity to the SAFOV acquisitions (16-min duration for a 106 cm FOV) were obtained on the LAFOV in 1.63 ± 0.19 min (mean ± standard error). Equivalent SNR was obtained by 1.82 ± 1.00 min LAFOV acquisitions. No statistically significant differences (p 0.05) in TBR were observed even for 0.5 min LAFOV examinations. Subjective image quality rated by two physicians confirmed the 10 min LAFOV to be of the highest quality, with equivalence between the LAFOV and the SAFOV at 1.8 ± 0.85 min. By analogy, if the LAFOV scans were maintained at 10 min, proportional reductions in applied radiopharmaceutical could obtain equivalent lesion integral activity for activities under 40 MBq and equivalent doses for the PET component of1 mSv.Improved image quality, lesion quantification and SNR resulting from higher sensitivity were demonstrated for an LAFOV system in a head-to-head comparison under clinical conditions. The LAFOV system could deliver images of comparable quality and lesion quantification in under 2 min, compared to routine SAFOV acquisition (16 min for equivalent FOV coverage). Alternatively, the LAFOV system could allow for low-dose examination protocols. Shorter LAFOV acquisitions (0.5 min), while of lower visual quality and SNR, were of adequate quality with respect to target lesion identification, suggesting that ultra-fast or low-dose acquisitions can be acceptable in selected settings.

Purpose: To evaluate the performance of the Biograph Vision Quadra (Siemens Healthineers) PET/CT system. This new system is based on the Siemens Biograph Vision 600, using the same silicon photomultiplier-based detectors with 3.2��3.2��20-mm lutetium-oxoorthosilicate crystals. The Quadra's 32 detector rings provide a fourfold larger axial field of view (AFOV) of 106 cm, enabling imaging of major organs in one bed position. Methods: Physical performance of the scanner was evaluated according to the National Electrical Manufacturers Association NU 2-2018 standard with additional experiments to characterize energy resolution. Image quality was assessed with foreground to background ratios of 4:1 and 8:1. Additionally, a clinical 18F-FDG-PET study was reconstructed with varying frame durations. In all experiments, data were acquired using the Quadra's maximum ring distance of 322 crystals (MRD 322), while image reconstructions could only be performed with a maximum ring distance of 85 crystals rings (MRD 85). Results: The spatial resolution at full width half maximum in radial, tangential and axial directions were 3.3, 3.4 and 3.8 mm respectively. The sensitivity was 83 cps/kBq for MRD 85 and 176 cps/kBq for MRD 322. The NECRs at peak were 1613 kcps for MRD 85 and 2956 kcps for MRD 322, both at 27.5 kBq/mL. The respective scatter fractions at peak NECR equaled 36 % and 37 %. The TOF resolution at peak NECR was 228 ps for MRD 85 and 230 ps for MRD 322. Image contrast recovery ranged from 69.6% to 86.9 % for 4:1 contrast ratios and from 77.7 % to 92.6 % for 8:1 contrast ratios reconstructed using PSF-TOF with 8 iterations and 5 subsets. Thirty seconds frames provided readable lesion detectability and acceptable noise levels in clinical images. Conclusion: The Biograph Vision Quadra PET/CT has similar spatial and time resolution compared to the Biograph Vision 600 but exhibits improved sensitivity and NECR due to its extended AFOV. The reported spatial resolution, time resolution, and sensitivity makes it a competitive new device in the class of PET-scanners with extended AFOV.

OBJECTIVE To investigate the influence of colour scales on the interpretation of [68Ga]Ga-PSMA-11 PET/CT for the diagnosis of recurrent prostate cancer. METHODS 50 consecutive patients who underwent [68Ga]Ga-PSMA-11 PET/CT for recurrent prostate cancer were selected for this retrospective study. The scans were randomised, anonymised and read by five different readers first in the visually nonlinear colour scale 'PET-rainbow'. Scans were then rerandomised and read in the visually linear colour scale 'hot-metal new'. For each scan in each colour scale the numbers of pathological, equivocal and benign lesions were noted. Scans where the majority of readers (���3) reported at least one PET-positive lesion were recorded as 'pathological'. Patient-level sensitivity was obtained by composite standard with 14.8��������1.2���months of follow-up. RESULTS Increased numbers of lesions per patient were reported for all readers in PET-rainbow compared to hot-metal new (37.4��������15.2 vs. 33.9��������16.4, respectively, P���=���0.0005). On a per-patient basis, 43 scans were rated pathological in PET-rainbow, compared to 39 in hot-metal new. Follow-up was available for 30 patients confirming 26 pathological scans with positive follow-up in PET-rainbow, and 23 in hot-metal new. Three pathological scans were missed in hot-metal new. Patient-level sensitivity was higher for PET-rainbow (0.96) compared to hot-metal new (0.85). Inter-reader reliability was higher for hot-metal new (Fleiss �����=���0.76) compared to PET-rainbow (Fleiss �����=���0.60). CONCLUSION Use of PET-rainbow was associated with improved lesion detection and sensitivity compared to hot-metal new, although at cost of reduced inter-rater agreement. Consequently, the use of PET-rainbow for clinical routine and future studies involving [68Ga]Ga-PSMA-11 is recommended.

Purpose To investigate the performance of the new long axial field-of-view (LAFOV) Biograph Vision Quadra PET/CT and a standard axial field-of-view (SAFOV) Biograph Vision 600 PET/CT (both: Siemens Healthineers) system using an intra-patient comparison. Methods Forty-four patients undergoing routine oncological PET/CT were prospectively included and underwent a same-day dual-scanning protocol following a single administration of either 18F-FDG (n = 20), 18F-PSMA-1007 (n = 16) or 68Ga-DOTA-TOC (n = 8). Half the patients first received a clinically routine examination on the SAFOV (FOVaxial 26.3 cm) in continuous bed motion and then immediately afterwards on the LAFOV system (10-min acquisition in list mode, FOVaxial 106 cm); the second half underwent scanning in the reverse order. Comparisons between the LAFOV at different emulated scan times (by rebinning list mode data) and the SAFOV were made for target lesion integral activity, signal to noise (SNR), target lesion to background ratio (TBR) and visual image quality. Results Equivalent target lesion integral activity to the SAFOV acquisitions (16-min duration for a 106 cm FOV) were obtained on the LAFOV in 1.63 ± 0.19 min (mean ± standard error). Equivalent SNR was obtained by 1.82 ± 1.00 min LAFOV acquisitions. No statistically significant differences (p > 0.05) in TBR were observed even for 0.5 min LAFOV examinations. Subjective image quality rated by two physicians confirmed the 10 min LAFOV to be of the highest quality, with equivalence between the LAFOV and the SAFOV at 1.8 ± 0.85 min. By analogy, if the LAFOV scans were maintained at 10 min, proportional reductions in applied radiopharmaceutical could obtain equivalent lesion integral activity for activities under 40 MBq and equivalent doses for the PET component of Conclusion Improved image quality, lesion quantification and SNR resulting from higher sensitivity were demonstrated for an LAFOV system in a head-to-head comparison under clinical conditions. The LAFOV system could deliver images of comparable quality and lesion quantification in under 2 min, compared to routine SAFOV acquisition (16 min for equivalent FOV coverage). Alternatively, the LAFOV system could allow for low-dose examination protocols. Shorter LAFOV acquisitions (0.5 min), while of lower visual quality and SNR, were of adequate quality with respect to target lesion identification, suggesting that ultra-fast or low-dose acquisitions can be acceptable in selected settings.

Contains fulltext : 235569.pdf (Publisher’s version ) (Open Access) Medical imaging methods are assuming a greater role in the workup of patients with COVID-19, mainly in relation to the primary manifestation of pulmonary disease and the tissue distribution of the angiotensin-converting-enzyme 2 (ACE 2) receptor. However, the field is so new that no consensus view has emerged guiding clinical decisions to employ imaging procedures such as radiography, computer tomography (CT), positron emission tomography (PET), and magnetic resonance imaging, and in what measure the risk of exposure of staff to possible infection could be justified by the knowledge gained. The insensitivity of current RT-PCR methods for positive diagnosis is part of the rationale for resorting to imaging procedures. While CT is more sensitive than genetic testing in hospitalized patients, positive findings of ground glass opacities depend on the disease stage. There is sparse reporting on PET/CT with [(18)F]-FDG in COVID-19, but available results are congruent with the earlier literature on viral pneumonias. There is a high incidence of cerebral findings in COVID-19, and likewise evidence of gastrointestinal involvement. Artificial intelligence, notably machine learning is emerging as an effective method for diagnostic image analysis, with performance in the discriminative diagnosis of diagnosis of COVID-19 pneumonia comparable to that of human practitioners.

Over the past decade, the tumor microenvironment (TME) has become a new paradigm of cancer diagnosis and therapy due to its unique biological features, mainly the interconnection between cancer and stromal cells. Within the TME, cancer-associated fibroblasts (CAFs) demonstrate as one of the most critical stromal cells that regulate tumor cell growth, progression, immunosuppression, and metastasis. CAFs are identified by various biomarkers that are expressed on their surfaces, such as fibroblast activation protein (FAP), which could be utilized as a useful target for diagnostic imaging and treatment. One of the advantages of targeting FAP-expressing CAFs is the absence of FAP expression in quiescent fibroblasts, leading to a controlled targetability of diagnostic and therapeutic compounds to the malignant tumor stromal area using radiolabeled FAP-based ligands. FAP-based radiopharmaceuticals have been investigated strenuously for the visualization of malignancies and delivery of theranostic radiopharmaceuticals to the TME. This review provides an overview of the state of the art in TME compositions, particularly CAFs and FAP, and their roles in cancer biology. Moreover, relevant reports on radiolabeled FAP inhibitors until the year 2021 are highlighted—as well as the current limitations, challenges, and requirements for those radiolabeled FAP inhibitors in clinical translation.

The good efficacy of radioligand therapy (RLT) targeting prostate specific-membrane antigen (PSMA) for the treatment of metastatic castration-resistant prostate cancer (mCRPC) has been recently demonstrated in several clinical studies. However, the treatment effect of 177Lu-PSMA-ligands is still suboptimal for a significant fraction of patients. In contrast to external beam radiotherapy, the radiation dose distribution itself is strongly influenced by the heterogeneous tumour microenvironment. Although microdosimetry is critical for RLT treatment outcome, it is difficult to clinically or experimentally establish the quantitative relation. We propose an in silico approach to quantitatively investigate the microdosimetry and its influence on treatment outcome for PSMA-directed RLT of two different radioisotopes 177Lu and 225 Ac. The ultimate goal is optimize the combined 177 Lu and 225 Ac-PSMA therapy and maximize the anti-tumour effect, while minimizing irradiation of off-target tissues.Clinical relevance- With the proposed hybrid model we show that 177Lu-PSMA-ligands treatment assures a more homogeneously distributed dose and a lower dependency of the treatment outcome on the domain vascularisation. On the other hand, the 225Ac-PSMA-ligands treatment shows a much stronger efficacy in killing tumor cells with an equivalent mean dose distribution even in an hypoxic environment.

Purpose Amongst others, [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 are available for the detection of recurrent prostate cancer (rPC). There are currently limited data comparing the performance of these two radioligands with respect to clinical outcomes or their cost efficacy, which this study aims to address. Methods Two hundred and forty-four patients undergoing PSMA PET/CT for rPC were retrospectively analysed for this study (one hundred and twenty two with each radiopharmaceutical) to generate rates of PET positivity, negativity and unclear findings. Patients underwent follow-up to determine the rate of additional examinations and to confirm PET findings. A Markov chain decision analysis was implemented to model clinical decision-making processes and to analyse clinical performance of the two tracers. We determine their clinical cost efficacies using cost data from several countries where both radiotracers are in routine use. Results The PET positivity rate was non-significantly higher for [18F]PSMA-1007 compared to [68Ga]Ga-PSMA-11 (91.8% vs. 86.9%, p = 0.68), whereas the rate of uncertain findings was significantly greater (17.2% vs. 8.25%, p = 0.02). The probability of a true positive finding was higher for [68Ga]Ga-PSMA-11 (0.90, 95% CI 0.70-0.98) vs. [18F]PSMA-1007 (0.81, 95% CI 0.66–0.91). A significantly (p < 0.0001) higher PPV for [68Ga]Ga-PSMA-11 (0.99, 95% CI 0.99–1.0 vs. 0.86) was found compared to [18F]PSMA-1007 (0.86, 95% CI 0.82–1.00). Intervention efficacy analysis favoured [68Ga]Ga-PSMA-11, where the number needed to image (to achieve a true positive finding) was 10.58 and the number needed to image to harm (to achieve a false positive finding) was − 8.08. A cost efficacy analysis favours [68Ga]Ga-PSMA-11 in three of the four jurisdictions analysed where health economic data was available (Switzerland, Israel, Australia) and [18F]PSMA-1007 in one jurisdiction (Denmark). Conclusion The analysis reveals a non-significantly higher PET positivity rate for [18F]PSMA-1007, but finds significantly greater rates of uncertain findings and false positive findings when compared to [68Ga]Ga-PSMA-11. We find differences in the two tracers in terms of clinical performance and cost efficacy. The method presented herein is generalisable and can be used with clinical or cost data for other countries or tracers.