Publications by authors named "Clemens Mingels"

20 Publications

  • Page 1 of 1

Abbreviated scan protocols to capture F-FDG kinetics for long axial FOV PET scanners.

Eur J Nucl Med Mol Imaging 2022 Mar 12. Epub 2022 Mar 12.

Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Purpose: Kinetic parameters from dynamic F-fluorodeoxyglucose (FDG) imaging offer complementary insights to the study of disease compared to static clinical imaging. However, dynamic imaging protocols are cumbersome due to the long acquisition time. Long axial field-of-view (LAFOV) PET scanners (> 70 cm) have two advantages for dynamic imaging over clinical PET scanners with a standard axial field-of-view (SAFOV; 16-30 cm). The large axial coverage enables multi-organ dynamic imaging in a single bed position, and the high sensitivity may enable clinically routine abbreviated dynamic imaging protocols.

Methods: In this work, we studied two abbreviated protocols using data from a 65-min dynamic F-FDG scan: (A) dynamic imaging immediately post-injection (p.i.) for variable durations, and (B) dynamic imaging immediately p.i. for variable durations plus a 1-h p.i. (5-min-long) datapoint. Nine cancer patients were imaged on the Biograph Vision Quadra (Siemens Healthineers). Time-activity curves over the lesions (N = 39) were fitted using the Patlak graphical analysis and a 2-tissue-compartment (2C, k = 0) model for variable scan durations (5-60 min). Kinetic parameters from the complete dataset served as the reference. Lesions from all cancers were grouped into low, medium, and high flux groups, and bias and precision of K (Patlak) and K, K, k, and k (2C) were calculated for each group.

Results: Using only early dynamic data with the 2C (or Patlak) model, accurate quantification of K required at least 50 (or 55) min of dynamic data for low flux lesions, at least 30 (or 40) min for medium flux lesions, and at least 15 (or 20) min for high flux lesions to achieve both 10% bias and precision. The addition of the final (5-min) datapoint allowed for accurate quantification of K with a bias and precision of 10% using only 10-15 min of early dynamic data for either model.

Conclusion: Dynamic imaging for 10-15 min immediately p.i. followed by a 5-min scan at 1-h p.i can accurately and precisely quantify F-FDG on a long axial FOV scanner, potentially allowing for more widespread use of dynamic F-FDG imaging.
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http://dx.doi.org/10.1007/s00259-022-05747-3DOI Listing
March 2022

Diagnostic accuracy of [F]PSMA-1007 PET/CT in biochemical recurrence of prostate cancer.

Eur J Nucl Med Mol Imaging 2022 Jun 24;49(7):2436-2444. Epub 2022 Jan 24.

Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, Freiburgstr. 18, 3010, Bern, Switzerland.

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 [F]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 [F]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 [F]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.
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http://dx.doi.org/10.1007/s00259-022-05693-0DOI Listing
June 2022

Tumor microenvironment mechanisms and bone metastatic disease progression of prostate cancer.

Cancer Lett 2022 04 17;530:156-169. Epub 2022 Jan 17.

Department for BioMedical Research, Urology Research Laboratory, University of Bern, Bern, Switzerland. Electronic address:

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.
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http://dx.doi.org/10.1016/j.canlet.2022.01.015DOI Listing
April 2022

First results on kinetic modelling and parametric imaging of dynamic F-FDG datasets from a long axial FOV PET scanner in oncological patients.

Eur J Nucl Med Mol Imaging 2022 05 4;49(6):1997-2009. Epub 2022 Jan 4.

Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 18, 3010, Bern, Switzerland.

Purpose: To investigate the kinetics of F-fluorodeoxyglucose (F-FDG) by positron emission tomography (PET) in multiple organs and test the feasibility of total-body parametric imaging using an image-derived input function (IDIF).

Methods: Twenty-four oncological patients underwent dynamic F-FDG scans lasting 65 min using a long  axial FOV (LAFOV) PET/CT system. Time activity curves (TAC) were extracted from semi-automated segmentations of multiple organs, cerebral grey and white matter, and from vascular structures. The tissue and tumor lesion TACs were fitted using an irreversible two-tissue compartment (2TC) and a Patlak model. Parametric images were also generated using direct and indirect Patlak methods and their performances were evaluated.

Results: We report estimates of kinetic parameters and metabolic rate of glucose consumption (MR) for different organs and tumor lesions. In some organs, there were significant differences between MR values estimated using 2TC and Patlak models. No statistically significant difference was seen between MR values estimated using 2TC and Patlak methods in tumor lesions (paired t-test, P = 0.65). Parametric imaging showed that net influx (K) images generated using direct and indirect Patlak methods had superior tumor-to-background ratio (TBR) to standard uptake value (SUV) images (3.1- and 3.0-fold mean increases in TBR, respectively). Influx images generated using the direct Patlak method had twofold higher contrast-to-noise ratio in tumor lesions compared to images generated using the indirect Patlak method.

Conclusion: We performed pharmacokinetic modelling of multiple organs using linear and non-linear models using dynamic total-body F-FDG images. Although parametric images did not reveal more tumors than SUV images, the results confirmed that parametric imaging furnishes improved tumor contrast. We thus demonstrate the feasibility of total-body kinetic modelling and parametric imaging in basic research and oncological studies. LAFOV PET can enhance dynamic imaging capabilities by providing high sensitivity parametric images and allowing total-body pharmacokinetic analysis.
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http://dx.doi.org/10.1007/s00259-021-05623-6DOI Listing
May 2022

[Radiosynoviorthesis of the thumb's carpometacarpal joint].

Orthopade 2022 Jan 20;51(1):9-12. Epub 2021 Dec 20.

Klinik für Nuklearmedizin, Inselspital, Universitätsspital Bern, Universität von Bern, Freiburgstr. 18, 3010, Bern, Schweiz.

Radiosynoviorthesis (RSO) is an established therapeutic method for the local treatment of pain in aseptic joint inflammation (e.g. arthritis, activated osteoarthritis, synovitis). RSO can be used for the treatment of synovial membrane inflammation of the finger joints such as the thumb's carpometacarpal joint. The beta emitter Erbium-169 (Er-169) is injected into the joint space, which irradiates the inflamed synovialis, thereby leading to fibrosis and obliteration of the pain receptors of the synovial membrane. The chances of success in the treatment of the thumb's carpometacarpal joint by RSO are estimated to be 54-100% within 2-6 weeks after therapy.
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http://dx.doi.org/10.1007/s00132-021-04194-6DOI Listing
January 2022

Comparing the clinical performance and cost efficacy of [Ga]Ga-PSMA-11 and [F]PSMA-1007 in the diagnosis of recurrent prostate cancer: a Markov chain decision analysis.

Eur J Nucl Med Mol Imaging 2021 Nov 13. Epub 2021 Nov 13.

Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, CH-3010, Bern, Switzerland.

Purpose: Amongst others, [Ga]Ga-PSMA-11 and [F]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 [F]PSMA-1007 compared to [Ga]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 [Ga]Ga-PSMA-11 (0.90, 95% CI 0.70-0.98) vs. [F]PSMA-1007 (0.81, 95% CI 0.66-0.91). A significantly (p < 0.0001) higher PPV for [Ga]Ga-PSMA-11 (0.99, 95% CI 0.99-1.0 vs. 0.86) was found compared to [F]PSMA-1007 (0.86, 95% CI 0.82-1.00). Intervention efficacy analysis favoured [Ga]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 [Ga]Ga-PSMA-11 in three of the four jurisdictions analysed where health economic data was available (Switzerland, Israel, Australia) and [F]PSMA-1007 in one jurisdiction (Denmark).

Conclusion: The analysis reveals a non-significantly higher PET positivity rate for [F]PSMA-1007, but finds significantly greater rates of uncertain findings and false positive findings when compared to [Ga]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.
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http://dx.doi.org/10.1007/s00259-021-05620-9DOI Listing
November 2021

PSMA-Ligand Uptake in Disseminated Epidermoid Cysts in a PSMA PET/CT of a Patient With Recurrent Prostate Cancer.

Clin Nucl Med 2021 Dec;46(12):e598-e599

From the Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Abstract: 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.
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http://dx.doi.org/10.1097/RLU.0000000000003749DOI Listing
December 2021

FDG uptake in axillary lymph nodes after COVID-19 vaccination - a pitfall in a case of highly suspicious lymph node metastases of malignant melanoma.

Nuklearmedizin 2021 12 19;60(6):456-457. Epub 2021 Aug 19.

Inselspital, Bern University Hospital, Department of Nuclear Medicine, University of Bern, Bern, Switzerland.

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http://dx.doi.org/10.1055/a-1561-2046DOI Listing
December 2021

Feasibility of late acquisition [68Ga]Ga-PSMA-11 PET/CT using a long axial field-of-view PET/CT scanner for the diagnosis of recurrent prostate cancer-first clinical experiences.

Eur J Nucl Med Mol Imaging 2021 12 21;48(13):4456-4462. Epub 2021 Jun 21.

Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, Freiburgstr. 18, 3010, Bern, Switzerland.

Purpose: While acquisition of images in [ Ga]Ga-PSMA-11 following longer uptake times can improve lesion uptake and contrast, resultant imaging quality and count statistics are limited by the isotope's half-life (68 min). Here, we present a series of cases demonstrating that when performed using a long axial field-of-view (LAFOV) PET/CT system, late imaging is feasible and can even provide improved image quality compared to regular acquisitions.

Methods: In this retrospective case series, we report our initial experiences with 10 patients who underwent standard imaging at 1 h p.i. following administration of 192 ± 36 MBq [ Ga]Ga-PSMA-11 with additional late imaging performed at 4 h p.i. Images were acquired in a single bed position for 6 min at 1 h p.i. and 16 min p.i. at 4 h p.i. using a LAFOV scanner (106 cm axial FOV). Two experienced nuclear medicine physicians reviewed all scans in consensus and evaluated overall image quality (5-point Likert scale), lesion uptake in terms of standardised uptake values (SUV), tumour to background ratio (TBR) and target-lesion signal to background noise (SNR).

Results: Subjective image quality as rated on a 5-point Likert scale was only modestly lower for late acquisitions (4.2/5 at 4 h p.i.; 5/5 1 h p.i.), TBR was significantly improved (4 h: 3.41 vs 1 h: 1.93, p < 0.001) and SNR was improved with borderline significance (4 h: 33.02 vs 1 h: 24.80, p = 0.062) at later imaging. Images were obtained with total acquisition times comparable to routine examinations on standard axial FOV scanners.

Conclusion: Late acquisition in tandem with a LAFOV PET/CT resulted in improvements in TBR and SNR and was associated with only modest impairment in subjective visual imaging quality. These data show that later acquisition times for [ Ga]Ga-PSMA-11 may be preferable when performed on LAFOV systems.
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http://dx.doi.org/10.1007/s00259-021-05438-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566391PMC
December 2021

Authors' reply: PSMA-PET: is the time to say goodbye to metabolic radiopharmaceuticals in prostate cancer?

Eur J Nucl Med Mol Imaging 2021 07 4;48(8):2307-2308. Epub 2021 May 4.

Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, CH-3010, Bern, Switzerland.

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http://dx.doi.org/10.1007/s00259-021-05376-2DOI Listing
July 2021

A comprehensive review of imaging findings in COVID-19 - status in early 2021.

Eur J Nucl Med Mol Imaging 2021 07 1;48(8):2500-2524. Epub 2021 May 1.

Department of Diagnostic, Interventional and Pediatric Radiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

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 [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.
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http://dx.doi.org/10.1007/s00259-021-05375-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087891PMC
July 2021

The influence of digital PET/CT on diagnostic certainty and interrater reliability in [Ga]Ga-PSMA-11 PET/CT for recurrent prostate cancer.

Eur Radiol 2021 Oct 15;31(10):8030-8039. Epub 2021 Apr 15.

Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, Freiburgstr. 18, 3010, Bern, Switzerland.

Objective: To investigate the impact of digital PET/CT on diagnostic certainty, patient-based sensitivity and interrater reliability.

Methods: Four physicians retrospectively evaluated two matched cohorts of patients undergoing [Ga]Ga-PSMA-11 PET/CT on a digital (dPET/CT n = 65) or an analogue scanner (aPET/CT n = 65) for recurrent prostate cancer between 11/2018 and 03/2019. The number of equivocal and pathological lesions as well as the frequency of discrepant findings and the interrater reliability for the two scanners were compared.

Results: dPET/CT detected more lesions than aPET/CT (p < 0.001). A higher number of pathological scans were observed for dPET/CT (83% vs. 57%, p < 0.001). The true-positive rate at follow-up was 100% for dPET/CT compared to 84% for aPET/CT (p < 0.001). The proportion of lesions rated as non-pathological as a total of all PSMA-avid lesions detected for dPET/CT was comparable to aPET/CT (61.8% vs. 57.0%, p = 0.99). Neither a higher rate of diagnostically uncertain lesions (11.5% dPET/CT vs. 13.7% aPET/CT, p = 0.95) nor discrepant scans (where one or more readers differed in opinion as to whether the scan is pathological) were observed (18% dPET/CT vs. 17% aPET/CT, p = 0.76). Interrater reliability for pathological lesions was excellent for both scanner types (Cronbach's α = 0.923 dPET/CT; α = 0.948 aPET/CT) and interrater agreement was substantial for dPET/CT (Krippendorf's α = 0.701) and almost perfect in aPET/CT (α = 0.802).

Conclusions: A higher detection rate for pathological lesions for dPET/CT compared with aPET/CT in multiple readers was observed. This improved sensitivity was coupled with an improved true-positive rate and was not associated with increased diagnostic uncertainty, rate of non-specific lesions, or reduced interrater reliability.

Key Points: • New generation digital scanners detect more cancer lesions in men with prostate cancer. • When using digital scanners, the doctors are able to diagnose prostate cancer lesions with better certainty • When using digital scanners, the doctors do not disagree with each other more than with other scanner types.
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http://dx.doi.org/10.1007/s00330-021-07870-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452558PMC
October 2021

Clinical performance of long axial field of view PET/CT: a head-to-head intra-individual comparison of the Biograph Vision Quadra with the Biograph Vision PET/CT.

Eur J Nucl Med Mol Imaging 2021 07 2;48(8):2395-2404. Epub 2021 Apr 2.

Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, Freiburgstr. 18, 3010, Bern, Switzerland.

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 F-FDG (n = 20), F-PSMA-1007 (n = 16) or Ga-DOTA-TOC (n = 8). Half the patients first received a clinically routine examination on the SAFOV (FOV 26.3 cm) in continuous bed motion and then immediately afterwards on the LAFOV system (10-min acquisition in list mode, FOV 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 <1 mSv.

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.
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http://dx.doi.org/10.1007/s00259-021-05282-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241747PMC
July 2021

Correction to: Comparing the diagnostic performance of radiotracers in recurrent prostate cancer: a systematic review and network meta-analysis.

Eur J Nucl Med Mol Imaging 2021 Aug;48(9):3014-3016

Department of Nuclear Medicine. Inselspital, Bern University Hospital, University of Bern, Street: Freiburgstr. 18, CH-3010, Bern, Switzerland.

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http://dx.doi.org/10.1007/s00259-021-05300-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8496592PMC
August 2021

Digital PET/CT allows for shorter acquisition protocols or reduced radiopharmaceutical dose in [F]-FDG PET/CT.

Ann Nucl Med 2021 Apr 7;35(4):485-492. Epub 2021 Feb 7.

Department of Nuclear Medicine. Inselspital, Bern University Hospital, University of Bern, Freiburgstr. 18, 3010, Bern, Switzerland.

Purpose: To establish the feasibility of shorter acquisition times (and by analogy, applied activity) on tumour detection and lesion contrast in digital PET/CT.

Methods: Twenty-one randomly selected patients who underwent oncological [F]-FDG PET/CT on a digital PET/CT were retrospectively evaluated. Scan data were anonymously obtained and reconstructed in list-mode acquisition for a standard 2 min/bed position (bp), 1 min/bp and 30 s/bp (100%, 50% and 25% time or applied activity, respectively). Scans were randomized and read by two nuclear medicine physicians in a consensus read. Readers were blind to clinical details. Scans were evaluated for the number of pathological lesions detected. Measured uptake for lesions was evaluated by maximum and mean standardized uptake value (SUVmax and SUVmean, respectively) and tumour-to-backround ratio (TBR) were compared. Agreement between the three acquisitions was compared by Krippendorf's alpha.

Results: Overall n = 100 lesions were identified in the 2 min and 1 min/bp acquisitions and n = 98 lesions in the 30 s/bp acquisitions. Agreement between the three acquisitions with respect to lesion number and tumour-to-background ratio showed almost perfect agreement (K's α = 0.999). SUVmax, SUVmean and TBR likewise showed > 98% agreement, with longer acquisitions being associated with slightly higher mean TBR (2 min/bp 7.94 ± 4.41 versus 30 s/bp 7.84 ± 4.22, p < 0.05).

Conclusion: Shorter acquisition times have traditionally been associated with reduced lesion detectability or the requirement for larger amounts of radiotracer activity. These data confirm that this is not the case for new-generation digital PET scanners, where the known higher sensitivity results in clinically adequate images for shorter acquisitions. Only a small variation in the semi-quantitative parameters SUVmax, SUVmean and TBR was seen, confirming that either reduction of acquisition time or (by analogy) applied activity can be reduced as much as 75% in digital PET/CT without apparent clinical detriment.
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http://dx.doi.org/10.1007/s12149-021-01588-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981298PMC
April 2021

Comparing the diagnostic performance of radiotracers in recurrent prostate cancer: a systematic review and network meta-analysis.

Eur J Nucl Med Mol Imaging 2021 08 6;48(9):2978-2989. Epub 2021 Feb 6.

Department of Nuclear Medicine. Inselspital, Bern University Hospital, University of Bern, Street: Freiburgstr. 18, CH-3010, Bern, Switzerland.

Purpose: Many radiotracers are currently available for the detection of recurrent prostate cancer (rPC), yet many have not been compared head-to-head in comparative imaging studies. There is therefore an unmet need for evidence synthesis to guide evidence-based decisions in the selection of radiotracers. The objective of this study was therefore to assess the detection rate of various radiotracers for the rPC.

Methods: The PUBMED, EMBASE, and the EU and NIH trials databases were searched without date or language restriction for comparative imaging tracers for 13 radiotracers of principal interest. Key search terms included 18F-PSMA-1007, 18F-DCPFyl, 68Ga-PSMA-11, 18F-PSMA-11, 68Ga-PSMA-I&T, 68Ga-THP-PSMA, 64Cu-PSMA-617, 18F-JK-PSMA-7, 18F-Fluciclovine, 18F-FABC, 18F-Choline, 11C-Choline, and 68Ga-RM2. Studies reporting comparative imaging data in humans in rPC were selected. Single armed studies and matched pair analyses were excluded. Twelve studies with eight radiotracers were eligible for inclusion. Two independent reviewers screened all studies (using the PRISMA-NMA statement) for inclusion criteria, extracted data, and assessed risk of bias (using the QUADAS-2 tool). A network meta-analysis was performed using Markov-Chain Monte Carlo Bayesian analysis to obtain estimated detection rate odds ratios for each tracer combination.

Results: A majority of studies were judged to be at risk of publication bias. With the exception of 18F-PSMA-1007, little difference in terms of detection rate was revealed between the three most commonly used PSMA-radiotracers (Ga-PSMA-11, F-PSMA-1007, F-DCFPyl), which in turn showed clear superiority to choline and fluciclovine using the derived network.

Conclusion: Differences in patient-level detection rates were observed between PSMA- and choline-radiotracers. However, there is currently insufficient evidence to favour one of the four routinely used PSMA-radioligands (PSMA-11, PSMA-1007, PSMA-I&T, and DCFPyl) over another owing to the limited evidence base and risk of publication bias revealed by our systematic review. A further limitation was lack of reporting on diagnostic accuracy, which might favour radiotracers with low specificity in an analysis restricted only to detection rate. The NMA derived can be used to inform the design of future clinical trials and highlight areas where current evidence is weak.
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http://dx.doi.org/10.1007/s00259-021-05210-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263438PMC
August 2021

Combination of Forced Diuresis with Additional Late Imaging in Ga-PSMA-11 PET/CT: Effects on Lesion Visibility and Radiotracer Uptake.

J Nucl Med 2021 09 5;62(9):1252-1257. Epub 2021 Feb 5.

Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; and

Renal excretion of some prostate-specific membrane antigen (PSMA) ligands and consequently increased bladder activity can obscure locally relapsing prostate cancer lesions in PSMA PET/CT. Furthermore, additional late imaging in PSMA PET/CT provides a useful method to clarify uncertain findings. The aim of this retrospective study was to investigate a modified imaging protocol combining late additional imaging with hydration and forced diuresis in individuals undergoing additional late scanning for uncertain lesions or low prostate-specific antigen. We compared an older protocol with a newer one. In the old protocol, patients undergoing Ga-PSMA-11 PET/CT were examined at 90 min after injection, with 1 L of oral hydration beginning at 30 min after injection and 20 mg of furosemide given intravenously at 1 h after injection, followed by additional late imaging at 2.5 h after injection without further preparation. In the new protocol, a second group received the same procedure as before, with an additional 0.5 L of oral hydration and 10 mg of furosemide intravenously 30 min before the late imaging. We examined 132 patients (76 with the old protocol and 56 with the new one) with respect to urinary bladder activity (SUV), prostate cancer lesion uptake (SUV), and lesion contrast (ratio of tumor SUV to bladder SUV for local relapses and ratio of tumor SUV to gluteal-muscle SUV for nonlocal prostate cancer lesions). Bladder activity was significantly greater for the old protocol in the late scans than for the new protocol (ratio of bladder activity at 2.5 h to bladder activity at 1.5 h, 2.33 ± 1.17 vs. 1.37 ± 0.50, < 0.0001). Increased tumor SUV and contrast were seen at 2.5 h compared with 1.5 h ( < 0.0001 for old protocol; = 0.02 for new protocol). Increased bladder activity for the old protocol resulted in decreased lesion-to-bladder contrast, which was not the case for the new protocol. Tumor-to-background ratios increased at late imaging for both protocols, but the increase was significantly lower for the new protocol. For the old protocol, comparing the 1.5-h to the 2.5-h acquisitions, 4 lesions in 4 patients (4/76 = 5.2% of the cohort) were visible at the postdiuresis 1.5-h acquisition but not at 2.5 h, having been obscured as a result of the higher bladder activity. In the new protocol, 2 of 56 (3.6%) patients had lesions visible only at late imaging, and 2 patients had lesions that could be better discriminated at late imaging. Although the combination of diuretics and hydration can be a useful method to increase the visualization and detectability of locally recurrent prostate cancer in standard Ga-PSMA-11 PET/CT, their effects do not sufficiently continue into additional late imaging. Additional diuresis and hydration are recommended to improve the visibility, detection, and diagnostic certainty of local recurrences.
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http://dx.doi.org/10.2967/jnumed.120.257741DOI Listing
September 2021

Extended perfusion defects in lung perfusion-SPECT/CT in a case of fatal COVID-19 pneumonia.

Nuklearmedizin 2021 06 26;60(3):249-251. Epub 2021 Jan 26.

Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

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http://dx.doi.org/10.1055/a-1333-0226DOI Listing
June 2021

The influence of colour scale in lesion detection and patient-based sensitivity in [68Ga]Ga-PSMA-PET/CT.

Nucl Med Commun 2021 May;42(5):495-502

Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

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 κ = 0.76) compared to PET-rainbow (Fleiss κ = 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.
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http://dx.doi.org/10.1097/MNM.0000000000001364DOI Listing
May 2021

Incidental SARS-CoV-2-related findings in asymptomatic patients in [F]-FDG-PET/CT-potential insights.

Eur J Nucl Med Mol Imaging 2020 08 22;47(9):2068-2069. Epub 2020 May 22.

Department of Nuclear Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

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http://dx.doi.org/10.1007/s00259-020-04869-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244259PMC
August 2020
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