Publications by authors named "Ali Afshar-Oromieh"

93 Publications

Assessment of malignancy and PSMA expression of uncertain bone foci in [F]PSMA-1007 PET/CT for prostate cancer-a single-centre experience of PET-guided biopsies.

Eur J Nucl Med Mol Imaging 2022 Apr 28. Epub 2022 Apr 28.

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

Purpose: Uncertain focal bone uptake (UBU) with intensive radiopharmaceutical avidity are frequently observed in patients undergoing [F]PSMA-1007 PET/CT for the detection of prostate cancer (PC). Such foci can pose diagnostic conundrums and risk incorrect staging. The aim of this short communication is to share the results of PET-guided biopsies of such foci.

Methods: A retrospective analysis revealed 10 patients who were referred to our department for PET-guided biopsy of UBU visible in a previous [F]PSMA-1007 PET/CT. [F]-PSMA-1007 PET-guided biopsy was conducted for 11 PSMA-avid bone foci 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 foci.

Results: 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.

Conclusions: 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 [F]PSMA-1007 uptake of which the reason remains unclear. Readers must interpret such foci 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 foci.
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http://dx.doi.org/10.1007/s00259-022-05745-5DOI Listing
April 2022

EARL compliance measurements on the biograph vision Quadra PET/CT system with a long axial field of view.

EJNMMI Phys 2022 Apr 8;9(1):26. Epub 2022 Apr 8.

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

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 F 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 RC, RC, and RC, 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. RC 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 RC limits closer to unity would possibly even permit shorter frames.
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http://dx.doi.org/10.1186/s40658-022-00455-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8994003PMC
April 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

Radiolabeled PSMA Inhibitors.

Cancers (Basel) 2021 Dec 13;13(24). Epub 2021 Dec 13.

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

PSMA has shown to be a promising target for diagnosis and therapy (theranostics) of prostate cancer. We have reviewed developments in the field of radio- and fluorescence-guided surgery and targeted photodynamic therapy as well as multitargeting PSMA inhibitors also addressing albumin, GRPr and integrin αβ. An overview of the regulatory status of PSMA-targeting radiopharmaceuticals in the USA and Europe is also provided. Technical and quality aspects of PSMA-targeting radiopharmaceuticals are described and new emerging radiolabeling strategies are discussed. Furthermore, insights are given into the production, application and potential of alternatives beyond the commonly used radionuclides for radiolabeling PSMA inhibitors. An additional refinement of radiopharmaceuticals is required in order to further improve dose-limiting factors, such as nephrotoxicity and salivary gland uptake during endoradiotherapy. The improvement of patient treatment achieved by the advantageous combination of radionuclide therapy with alternative therapies is also a special focus of this review.
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http://dx.doi.org/10.3390/cancers13246255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699044PMC
December 2021

[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

In silico study on radiobiological efficacy of Ac-225 and Lu-177 for PSMA-guided radiotherapy.

Annu Int Conf IEEE Eng Med Biol Soc 2021 11;2021:4497-4500

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 Lu-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 Lu and Ac. The ultimate goal is optimize the combined Lu and 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 Lu-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 Ac-PSMA-ligands treatment shows a much stronger efficacy in killing tumor cells with an equivalent mean dose distribution even in an hypoxic environment.
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http://dx.doi.org/10.1109/EMBC46164.2021.9630297DOI Listing
November 2021

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

New Frontiers in Cancer Imaging and Therapy Based on Radiolabeled Fibroblast Activation Protein Inhibitors: A Rational Review and Current Progress.

Pharmaceuticals (Basel) 2021 Oct 5;14(10). Epub 2021 Oct 5.

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

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.
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http://dx.doi.org/10.3390/ph14101023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540221PMC
October 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

Performance Characteristics of the Biograph Vision Quadra PET/CT System with a Long Axial Field of View Using the NEMA NU 2-2018 Standard.

J Nucl Med 2022 Mar 22;63(3):476-484. Epub 2021 Jul 22.

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

Our purpose was to evaluate the performance of the Biograph Vision Quadra PET/CT system. This new system is based on the Biograph Vision 600, using the same silicon photomultiplier-based detectors with 3.2 × 3.2 × 20 mm lutetium-oxoorthosilicate crystals. The 32 detector rings of the Quadra provide a 4-fold larger axial field of view (AFOV) of 106 cm, enabling imaging of major organs in 1 bed position. The 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 F-FDG PET study was reconstructed with varying frame durations. In all experiments, data were acquired using the maximum ring distance of 322 crystals (MRD 322), whereas image reconstructions could be performed with a maximum ring distance of only 85 crystals (MRD 85). The spatial resolution at full width at half maximum in the radial, tangential, and axial directions was 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 noise-equivalent count rates (NECRs) at peak were 1,613 kcps for MRD 85 and 2,956 kcps for MRD 322, both at 27.49 kBq/mL. The respective scatter fractions at peak NECR equaled 36% and 37%. The time-of-flight 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 point-spread function time of flight with 8 iterations and 5 subsets. Thirty-second frames provided readable lesion detectability and acceptable noise levels in clinical images. The Biograph Vision Quadra PET/CT device has spatial and time resolution similar to those of the Biograph Vision 600 but exhibits improved sensitivity and NECR because of its extended AFOV. The reported spatial resolution, time resolution, and sensitivity make it a competitive new device in the class of PET scanners with an extended AFOV.
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http://dx.doi.org/10.2967/jnumed.121.261972DOI Listing
March 2022

Is Hypoxia a Factor Influencing PSMA-Directed Radioligand Therapy?-An In Silico Study on the Role of Chronic Hypoxia in Prostate Cancer.

Cancers (Basel) 2021 Jul 8;13(14). Epub 2021 Jul 8.

Department of Nuclear Medicine, Inselspital, University of Bern, 3010 Bern, Switzerland.

Radioligand therapy (RLT) targeting prostate specific-membrane antigen (PSMA) is an emerging treatment for metastatic castration-resistant prostate cancer (mCRPC). It administrates 225Ac- or 177Lu-labeled ligands for the targeted killing of tumor cells. Differently from X- or γ-ray, for the emitted α or β particles the ionization of the DNA molecule is less dependent on the tissue oxygenation status. Furthermore, the diffusion range of electrons in a tumor is much larger than the volume typically spanned by hypoxic regions. Therefore, hypoxia is less investigated as an influential factor for PSMA-directed RLT, in particular with β emitters. This study proposes an in silico approach to theoretically investigate the influence of tumor hypoxia on the PSMA-directed RLT. Based on mice histology images, the distribution of the radiopharmaceuticals was simulated with an in silico PBPK-based convection-reaction-diffusion model. Three anti-CD31 immunohistochemistry slices were used to simulate the tumor microenvironment. Ten regions of interest with varying hypoxia severity were analyzed. A kernel-based method was developed for dose calculation. The cell survival probability was calculated according to the linear-quadratic model. The statistical analysis performed on all the regions of interest (ROIs) shows more heterogeneous dose distributions obtained with 225Ac compared to 177Lu. The higher homogeneity of 177Lu-PSMA-ligand treatment is due to the larger range covered by the emitted β particles. The dose-to-tissue histogram (DTH) metric shows that in poorly vascularized ROIs only 10% of radiobiological hypoxic tissue receives the target dose using 177Lu-PSMA-ligand treatment. This percentage drops down to 5% using 225Ac. In highly vascularized ROIs, the percentage of hypoxic tissue receiving the target dose increases to more than 85% and 65% for the 177Lu and 225Ac-PSMA-ligands, respectively. The in silico study demonstrated that the reduced vascularization of the tumor strongly influences the dose delivered by PSMA-directed RLT, especially in hypoxic regions and consequently the treatment outcome.
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http://dx.doi.org/10.3390/cancers13143429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307065PMC
July 2021

Cystic Hepatic Neuroendocrine Tumor: A Rare Entity.

Clin Nucl Med 2021 Dec;46(12):e577-e578

From the Departments of Diagnostic, Interventional, and Pediatric Radiology.

Abstract: A 70-year-old man presented with unspecific abdominal symptoms and weight loss was referred for a sonographic examination. Sonography revealed 3 cystic hepatic masses in an otherwise unremarkable liver. Contrast-enhanced MRI of the liver was performed to characterize the hepatic lesions and elucidate their etiology. The differential diagnosis was primarily parasitic disease or metastases with cystic transformations. 68Ga-DOTATOC PET/CT revealed the neuroendocrine origin of these lesions, confirmed by biopsy. However, the primary site of the neuroendocrine tumor remained unclear, leaving primary hepatic neuroendocrine tumor and neuroendocrine cancer of unknown primary as possible diagnostic options.
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http://dx.doi.org/10.1097/RLU.0000000000003803DOI 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

Prostate Cancer Theranostics: PSMA Targeted Therapy.

PET Clin 2021 Jul;16(3):391-396

Department of Nuclear Medicine, University Hospital Münster, Münster, Germany; West German Cancer Center (WTZ). Electronic address:

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-I&T (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.
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http://dx.doi.org/10.1016/j.cpet.2021.03.004DOI Listing
July 2021

Prostate Cancer Theranostics: From Target Description to Imaging.

PET Clin 2021 Jul;16(3):383-390

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

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.
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http://dx.doi.org/10.1016/j.cpet.2021.03.003DOI Listing
July 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

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

Performance of [Ga]Ga-PSMA-11 PET/CT in patients with recurrent prostate cancer after prostatectomy-a multi-centre evaluation of 2533 patients.

Eur J Nucl Med Mol Imaging 2021 08 4;48(9):2925-2934. Epub 2021 Feb 4.

Department of Nuclear Medicine, Technical University of Munich, Munich, Germany.

Purpose: To evaluate the performance of [Ga]Ga-PSMA-11 PET/CT in the diagnosis of recurrent prostate cancer (PC) after prostatectomy in a large multicentre cohort.

Methods: The centres, which contributed to this study, were the departments of nuclear medicine of Heidelberg (Germany), Technical University of Munich (Germany) and Albert Einstein Hospital of São Paulo (Brazil). A total of 2533 patients who were scanned with [Ga]Ga-PSMA-11 PET/CT at 1 h p.i. due to recurrent PC after prostatectomy were included in this retrospective analysis. Exclusion criteria were as follows: patients with untreated primary tumour, previous chemotherapy or Xofigo®; those previously treated with exclusively external beam radiation therapy or HIFU; those referred for PSMA-therapy; and those treated with ADT (including first- and second-generation ADT) within the last 6 months. Potential influences of different factors such as PSA level, PSA doubling-time (PSA), PSA velocity (PSA), Gleason Score (GSC, including the separate analysis of 7a and 7b), age and amount of injected tracer were evaluated in a multivariable analysis.

Results: The rate of pathologic PET/CT-scans was 43% for PSA ≤ 0.2 ng/ml, 58% for PSA > 0.2 to ≤ 0.5, 72% for PSA > 0.5 to ≤ 1.0 and increased to a maximum of 93% for PSA > 10 ng/ml. A pathological PET/CT was significantly (p = 0.001) associated with PSA level and higher GSC. Amount of injected tracer, age, PSA and PSA were not associated with a higher probability of a pathological scan.

Conclusion: [Ga]Ga-PSMA-11 PET/CT at 1 h p.i. confirmed its high performance in the largest patient cohort yet analysed. Tumour detection showed a clear association with higher PSA and higher GSC. No association was found between a pathological [Ga]Ga-PSMA-11 PET/CT and age, amount of injected tracer, PSA or PSA.
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http://dx.doi.org/10.1007/s00259-021-05189-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263399PMC
August 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

Do fasting or high caloric drinks affect the physiological uptake of fluorine-18 prostate-specific membrane antigen-1007 in liver and bowel?

World J Nucl Med 2020 Jul-Sep;19(3):220-223. Epub 2019 Nov 7.

Department of Nuclear Medicine, University Hospital Münster, Münster, Germany.

Recently introduced fluorine-18 prostate-specific membrane antigen-1007 (F-PSMA-1007) for imaging prostate cancer has an intense physiologic liver uptake and biliary excretion. The aim of the present study was to evaluate the effect of different dietary conditions on this physiological uptake. Forty consecutive prostate cancer patients were scanned with F-PSMA-1007 positron emission tomography/computed tomography at different dietary conditions. In addition to a blinded read scoring, tracer uptake intensities (standardized uptake values [SUVs]) were measured in the liver and small bowel. There was no significant difference in liver and small-bowel uptake between different patient groups. Wilcoxon signed-rank tests revealed no significant difference of the median mean SUV of the liver or maximum SUV of the horizontal part of the duodenum between different dietary conditions groups. A dietary preparation of patients by fasting or the attempt to clear liver activity by high caloric drinks does not have a significant effect on tracer uptake in the liver or in the small bowel.
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http://dx.doi.org/10.4103/wjnm.WJNM_6_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745857PMC
November 2019

Effect of the versatile bifunctional chelator AAZTA on the radiometal labelling properties and the in vitro performance of a gastrin releasing peptide receptor antagonist.

EJNMMI Radiopharm Chem 2020 Nov 30;5(1):29. Epub 2020 Nov 30.

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

Background: Gastrin Releasing Peptide receptor (GRPr)-based radioligands have shown great promise for diagnostic imaging of GRPr-positive cancers, such as prostate and breast. The present study aims at developing and evaluating a versatile GRPr-based probe for both PET/SPECT imaging as well as intraoperative and therapeutic applications. The influence of the versatile chelator AAZTA on the radiometal labelling properties and the in vitro performance of the generated radiotracers were thoroughly investigated. The GRPr-based antagonist D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH was functionalized with the chelator 6-[Bis (carboxymethyl)amino]-1,4-bis (carboyxmethyl)-6-methyl-1,4-diazepane (AAZTA) through the spacer 4-amino-1-carboxymethyl-piperidine (Pip) to obtain AAZTA-Pip-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH (LF1). LF1 was radiolabelled with gallium-68 (PET), indium-111 (SPECT, intraoperative applications) and lutetium-177 (therapy, SPECT). In vitro evaluation included stability studies, determination of lipophilicity, protein-binding studies, determination of K and B as well as internalization studies using the epithelial human prostate cancer cell line PC3. In vitro monotherapy as well as combination therapy studies were further performed to assess its applicability as a theranostic compound.

Results: LF1 was labelled with gallium-68, indium-111 and lutetium-177 within 5 min at room temperature (RT). The apparent molar activities (A) were ranging between 50 and 60 GBq/μmol for the Ga-labelled LF1, 10-20 GBq/μmol for the In- and Lu-labelled LF1. The radiotracers were stable for a period of 4 h post labeling exhibiting a hydrophilic profile with an average of a LogD of - 3, while the bound activity to the human serum protein was approximately 10%. Ga-LF1, Lu-LF1 and In-LF1 exhibited high affinity for the PC3 cells, with K values of 16.3 ± 2.4 nM, 10.3 ± 2.73 nM and 5.2 ± 1.9 nM, respectively, and the required concentration of the radiotracers to saturate the receptors (B) was between 0.5 and 0.8 nM which corresponds to approximately 4 × 10 receptors per cell. Low specific internalization rate was found in cell culture, while the total specific cell surface bound uptake always exceeded the internalized activity. In vitro therapy studies showed that inhibition of PC3 cells growth is somewhat more efficient when combination of Lu-labelled LF1 with rapamycin is applied compared to Lu-laballed LF1 alone.

Conclusion: Encouraged by these promising in vitro data, preclinical evaluation of the LF1 precursor are planned in tumour models in vivo.
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http://dx.doi.org/10.1186/s41181-020-00115-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704979PMC
November 2020
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