Surgical radioguidance with beta-emitting radionuclides; challenges and possibilities: A position paper by the EANM.

Radioguidance that makes use of ß-emitting radionuclides is gaining in popularity and could have potential to strengthen the range of existing radioguidance techniques. While there is a strong tendency to develop new PET radiotracers, due to favorable imaging characteristics and the success of theranostics research, there are practical challenges that need to be overcome when considering use of ß-emitters for surgical radioguidance. In this position paper, the EANM identifies the possibilities and challenges that relate to the successful implementation of ß-emitters in surgical guidance, covering aspects related to instrumentation, radiation protection, and modes of implementation.

Biodistribution and radiation dosimetry of 124I-mIBG in adult patients with neural crest tumours and extrapolation to paediatric models.

AIM: Positron emission tomography (PET) using 124I-mIBG has been established for imaging and pretherapeutic dosimetry. Here, we report the first systematic analysis of the biodistribution and radiation dosimetry of 124I-mIBG in patients with neural crest tumours and project the results to paediatric patient models. METHODS: Adult patients with neural crest tumours who underwent sequential 124I-mIBG PET were included in this retrospective single-center analysis. PET data were acquired 4, 24, 48, and/or 120 h after administration of a mean of 43 MBq 124I-mIBG. Whole-body counting and blood sampling were performed at 2, 4, 24, 48 and 120 h after administration. Absorbed organ dose and effective dose coefficients were estimated in OLINDA/EXM 2.2 according to the MIRD formalism. Extrapolation to paediatric models was performed based on mass-fraction scaling of the organ-specific residence times. Biodistribution data for adults were also projected to 123I-mIBG and 131I-mIBG. RESULTS: Twenty-one patients (11 females, 10 males) were evaluated. For adults, the organs exposed to the highest dose per unit administered activity were urinary bladder (1.54 ± 0.40 mGy/MBq), salivary glands (0.77 ± 0.28 mGy/MBq) and liver (0.65 ± 0.22 mGy/MBq). Mean effective dose coefficient for adults was 0.25 ± 0.04 mSv/MBq (male: 0.24 ± 0.03 mSv/MBq, female: 0.26 ± 0.06 mSv/MBq), and increased gradually to 0.29, 0.44, 0.69, 1.21, and 2.94 mSv/MBq for the 15-, 10-, 5-, 1-years-old, and newborn paediatric reference patients. Projected mean effective dose coefficients for 123I-mIBG and 131I-mIBG for adults were 0.014 ± 0.002 mSv/MBq and 0.18 ± 0.04 mSv/MBq, respectively. CONCLUSION: PET-based derived radiation dosimetry data for 124I-mIBG from this study agreed well with historical projected data from ICRP 53. The effective dose coefficients presented here may aid in guidance for establishing weight-based activity administration protocols.

Quantification performance of silicon photomultiplier-based PET for small 18F-, 68Ga- and 124I-avid lesions in the context of radionuclide therapy planning.

PURPOSE: The aim of this study was to investigate conditions for reliable quantification of sub-centimeter lesions with low18F,68Ga, and124I uptake using a silicon photomultiplier-based PET/CT system. METHODS: A small tumor phantom was investigated under challenging but clinically realistic conditions resembling prostate and thyroid cancer lymph node metastases (6 spheres with 3.7-9.7 mm in diameter, 9 different activity concentrations ranging from about 0.25-25 kBq/mL, and a signal-to-background ratio of 20). Radionuclides with different positron branching ratios and prompt gamma coincidence contributions were investigated. Maximum-, contour-, and oversize-based partial volume effect (PVE) correction approaches were applied. Detection and quantification performance were estimated, considering a ±30 % deviation between imaged-derived and true activity concentrations as acceptable. A standard and a prolonged acquisition time and two image reconstruction algorithms (time-of-flight with/without point spread function modelling) were analyzed. Clinical data were evaluated to assess agreement of PVE-correction approaches indicating lesion quantification validity. RESULTS: The smallest 3.7-mm sphere was not visible. If the lesions were clearly observed, quantification was, except for a few cases, acceptable using contour- or oversized-based PVE-corrections. Quantification accuracy did not substantially differ between 18F, 68Ga, and 124I. No systematic differences between the analyzed reconstruction algorithms or shorter and larger acquisition times were observed. In the clinical evaluation of 20 lesions, an excellent statistical agreement between oversize- and contour-based PVE-corrections was observed. CONCLUSIONS: At the lower end of size (<10 mm) and activity concentration ranges of lymph-node metastases, quantification with reasonable accuracy is possible for 18F, 68Ga, and 124I, possibly allowing pre-therapeutic lesion dosimetry and individualized radionuclide therapy planning.

Reduction of emission time for [68Ga]Ga-PSMA PET/CT using the digital biograph vision: a phantom study.

BACKGROUND: The aim of this phantom study was to optimize the [68Ga]Ga-PSMA PET/CT examination in terms of scan time duration and image reconstruction parameters, in combination with PSF and TOF modelling, in a digital Biograph Vision PET/CT scanner. METHODS: Three types of phantoms were used: 1) soft-tissue tumor phantom consisting of six spheres mounted in a torso phantom; 2) bone-lung tumor phantom; 3) resolution phantom. Phantom inserts were filled with activity concentrations (ACs) that were derived from clinical data. Phantom data were acquired in list-mode at one bed position. Images with emission data ranging from 30 to 210 s in 30-s increments were reconstructed from a reference image acquired with 3.5-min emission. Iterative image reconstruction (OSEM), point-spread-function (PSF) and time-of-flight (TOF) options were applied using different iterations, Gaussian filters, and voxel sizes. The criteria for image quality was lesion detectability and lesion quantification, evaluated as contrast-to-noise ratio (CNR) and maximum AC (peak AC), respectively. A threshold value of CNR above 6 and percentage maximum AC (peak AC) deviation range of ±20% of the reference image were considered acceptable. The proposed single-bed scan time reduction was projected to a whole-body examination (patient validation scan) using the continuous-bed-motion mode. RESULTS: Sphere and background ACs of 20 kBq/mL and 1 kBq/mL were selected, respectively. The optimized single-bed scan time was approximately 60 s using OSEM-TOF or OSEM-TOF+PSF (four iterations, 4.0-mm Gaussian filter and almost isotropic voxel size of 3.0-mm side length), resulting in a PET spatial resolution of 6.3 mm for OSEM-TOF and 5.5 mm for OSEM-TOF+PSF. In the patient validation, the maximum percentage difference in lesion quantification between standard and optimized protocol (whole-body scan time of 15 vs. 5 min) was below 19%. CONCLUSIONS: A reduction of single-bed and whole-body scan time for [68Ga]Ga-PSMA PET/CT compared to current recommended clinical acquisition protocols is postulated. Clinical studies are warranted to validate the applicability of this protocol.

Quantitative 99mTc-DPD-SPECT/CT assessment of cardiac amyloidosis.

INTRODUCTION: Transthyretin (ATTR) amyloidosis is responsible for the majority of cardiac amyloidosis (CA) cases and can be reliably diagnosed with bone scintigraphy and the visual Perugini score. We aimed to implement a quantification method of cardiac amyloid deposits in patients with suspected cardiac amyloidosis and to compare performance to visual scoring. METHODS AND MATERIALS: 136 patients received 99mTc-DPD-bone scintigraphy including SPECT/CT of the thorax in case of suspicion of cardiac amyloidosis. Imaging phantom studies were performed to determine the scaling factor for standardized uptake value (SUV) quantification from SPECT/CT. Myocardial tracer uptake was quantified in a whole heart volume of interest. RESULTS: Forty-five patients were diagnosed with CA. A strong relationship between cardiac SUVmax and Perugini score was found (Spearman r 0.75, p < 0.0001). Additionally, tracer uptake in bone decreased with increasing cardiac SUVmax and Perugini score (p < 0.0001). ROC analysis revealed good performance of the SUVmax for the detection of ATTR-CA with AUC of 0.96 ± 0.02 (p < 0.0001) with sensitivity 98.7% and specificity 87.2%. CONCLUSION: We demonstrate an accessible and accurate quantitative SPECT approach in CA. Quantitative assessment of the cardiac tracer uptake may improve diagnostic accuracy and risk classification. This method may enable monitoring and assessment of therapy response in patients with ATTR amyloidosis.

PSMA-Directed Imaging and Therapy of Salivary Gland Tumors: A Single-Center Retrospective Study.

We analyzed the diagnostic performance of prostate-specific membrane antigen (PSMA) PET/CT and the dosimetry, efficacy, and safety of 177Lu-PSMA-617 radioligand therapy (RLT) in salivary gland malignancies (SGMs). Methods: We identified 28 SGM patients with PSMA PET/CT from our database. CT and PSMA PET/CT images were evaluated separately by 3 masked readers in joint reading sessions. Pathologic findings were grouped into 6 TNM regions, and lesion-based disease extent was classified as no disease (n = 1, 4%), unifocal (n = 2, 7%), oligometastatic (n = 9, 32%), multifocal (n = 3, 11%), or disseminated (n = 13, 47%). For each region, the SUVmax of the lesion with the highest uptake was measured and the visual PSMA expression score was evaluated on a per-patient basis using PROMISE criteria. The association between PSMA expression and clinical and histopathologic markers was tested using the Student t test. Five patients underwent PSMA RLT with intratherapeutic dosimetry. Response was assessed using RECIST 1.1, and adverse events were graded according to version 5.0 of the Common Terminology Criteria for Adverse Events. Results: Compared with CT, PSMA PET/CT demonstrated additional metastatic lesions in 11 of 28 (39%) patients, leading to upstaging of TNM and lesion-based disease extent in 3 (11%) and 6 (21%) patients, respectively. PSMA PET/CT detected CT-occult local tumor, regional lymph nodes, nonregional lymph nodes, and bone metastases in 1 (4%), 4 (14%), 2 (7%), and 4 (14%) patients, respectively; no additional lesions were detected in the other predefined regions. PSMA expression level was higher than liver in 6 patients (25%). A significantly higher SUVmax was observed in male than female patients (15.8 vs. 8.5, P = 0.007) and in bone than lung lesions (14.2 vs. 6.4, P = 0.006). PSMA RLT was discontinued after 1 cycle in 3 of 5 patients because of insufficient tumor doses. No adverse events of grade 4 or higher occurred. Conclusion: In SGMs, PSMA PET/CT demonstrated a superior detection rate and led to upstaging in about one third of patients when compared with CT. The male sex and the presence of bone metastases were associated with significantly higher PSMA expression. PSMA RLT was well tolerated, but most patients did not have more than 1 cycle because of insufficient tumor doses.

Phantom-based acquisition time and image reconstruction parameter optimisation for oncologic FDG PET/CT examinations using a digital system.

BACKGROUND: New-generation silicon-photomultiplier (SiPM)-based PET/CT systems exhibit an improved lesion detectability and image quality due to a higher detector sensitivity. Consequently, the acquisition time can be reduced while maintaining diagnostic quality. The aim of this study was to determine the lowest 18F-FDG PET acquisition time without loss of diagnostic information and to optimise image reconstruction parameters (image reconstruction algorithm, number of iterations, voxel size, Gaussian filter) by phantom imaging. Moreover, patient data are evaluated to confirm the phantom results. METHODS: Three phantoms were used: a soft-tissue tumour phantom, a bone-lung tumour phantom, and a resolution phantom. Phantom conditions (lesion sizes from 6.5 mm to 28.8 mm in diameter, lesion activity concentration of 15 kBq/mL, and signal-to-background ratio of 5:1) were derived from patient data. PET data were acquired on an SiPM-based Biograph Vision PET/CT system for 10 min in list-mode format and resampled into time frames from 30 to 300 s in 30-s increments to simulate different acquisition times. Different image reconstructions with varying iterations, voxel sizes, and Gaussian filters were probed. Contrast-to-noise-ratio (CNR), maximum, and peak signal were evaluated using the 10-min acquisition time image as reference. A threshold CNR value ≥ 5 and a maximum (peak) deviation of ± 20% were considered acceptable. 20 patient data sets were evaluated regarding lesion quantification as well as agreement and correlation between reduced and full acquisition time standard uptake values (assessed by Pearson correlation coefficient, intraclass correlation coefficient, Bland-Altman analyses, and Krippendorff's alpha). RESULTS: An acquisition time of 60 s per bed position yielded acceptable detectability and quantification results for clinically relevant phantom lesions ≥ 9.7 mm in diameter using OSEM-TOF or OSEM-TOF+PSF image reconstruction, a 4-mm Gaussian filter, and a 1.65 × 1.65 x 2.00-mm3 or 3.30 × 3.30 x 3.00-mm3 voxel size. Correlation and agreement of patient lesion quantification between full and reduced acquisition times were excellent. CONCLUSION: A threefold reduction in acquisition time is possible. Patients might benefit from more comfortable examinations or reduced radiation exposure, if instead of the acquisition time the applied activity is reduced.

Safety and Efficacy of 90Y-FAPI-46 Radioligand Therapy in Patients with Advanced Sarcoma and Other Cancer Entities.

PURPOSE: We report efficacy and safety of 90Y-labeled FAPI-46 (90Y-FAPI-46-RLT) in patients with advanced sarcoma, pancreatic cancer, and other cancer entities. EXPERIMENTAL DESIGN: Up to four cycles of radioligand therapy (RLT) were offered to patients with (i) progressive metastatic malignancy, (ii) exhaustion of approved therapies, and (iii) high fibroblast activation protein (FAP) expression, defined as SUVmax ≥ 10 in more than 50% of tumor. Primary endpoint was RECIST response after RLT. Secondary endpoints included PET response (PERCIST), overall survival (OS), dosimetry, and safety of FAP-RLT. RESULTS: Among 119 screened patients, 21 (18%) were found eligible [n = 16/3/1/1 sarcoma/pancreatic cancer/prostate/gastric cancer; 38% Eastern Cooperative Oncology Group (ECOG) ≥ 2] and received 47 90Y-FAPI-46-RLT cycles; 16 of 21 (76%) patients underwent repeat RLT. By RECIST, disease control was confirmed in 8 of 21 patients [38%; 8/16 (50%) of evaluable patients). There was one partial response (PR) and seven stable diseases after RLT. Disease control was associated with prolonged OS (P = 0.013). PERCIST response was noted in 8 of 21 patients [38%; 8/15 (53%) of evaluable patients]. Dosimetry was acquired in 19 (90%) patients. Mean absorbed dose was 0.53 Gy/GBq in kidney, 0.04 Gy/GBq in bone marrow, and <0.14 Gy/GBq in liver and lung. Treatment-related grade 3 or 4 adverse events were observed in 8 (38%) patients with thrombocytopenia (n = 6) and anemia (n = 6) being most prevalent. CONCLUSIONS: 90Y-FAPI-46-RLT was safe and led to RECIST PR in one case as well as stable disease in about one third of patients with initially progressive sarcomas, pancreatic cancer, and other cancers. Discontinuation after the first cycle and a low rate of PR requires future improvement of FAP-RLT.

Prostate specific membrane antigen-radio guided surgery using Cerenkov luminescence imaging-utilization of a short-pass filter to reduce technical pitfalls.

BACKGROUND: Intraoperative Cerenkov luminescence imaging (CLI) is a novel technique to assess surgical margins in patients undergoing nerve sparing radical prostatectomy (RP). Here, we analyze the efficacy of a 550-nm optical short-pass filter (OF) to improve its performance. METHODS: In this prospective single-center feasibility study ten patients with prostate cancer (PC) were included between December 2019 and April 2020, including three patients without tracer injection as a control group. After preoperative injection of 68-Ga-prostate-specific membrane antigen (PSMA)-11 followed by RP, CLI of the excised prostate and the incised index lesion was performed to visualize the primary tumor lesion. We compared the findings on intraoperative CLI to postoperative histopathology. Furthermore, CLI-intensities determined as tumor to background ratio (TBR) and contrast to noise ratio (CNR) were measured. RESULTS: Histopathology proved positive surgical margins (PSM) in 3 patients with corresponding findings in CLI. After magnetic resonance imaging (MRI)-informed incision above the index lesion 2 out of 3 prostates demonstrated elevated CLI signals with histopathological confirmation of PC cells. The use of the OF enabled a significant reduction of the area of the regions of interest from a median of 1.80 to 0.15 cm2 (reduction by 85%, P=0.005) leading to increased specificity. Signals due to PSMs were not suppressed by the 550-nm OF. The median TBR was reduced from 3.33 to 2.10. In all three patients of the control group elevated CLI intensities were detected at locations with diathermal energy deposition during surgery. After application of the 550-nm OF these were almost totally suppressed with a TBR of 1.10. Measurements of Cerenkov luminescence intensity with the 550-nm OF showed a significant Pearson's correlation of 0.82 between PSM and the elevated TBR (P=0.003) and a significant Pearson's correlation of 0.66 between PSM and elevated CNR (P=0.04). Measurements without the OF did not correlate significantly. CONCLUSIONS: Intraoperative 68-Ga-PSMA CLI in PC is a tool that warrants further investigation to visualize PSM especially in intermediate and high-risk PC. Intraoperative CLI benefits from usage of a 550-nm OF to reduce false-positive signals.

Silicon-photomultiplier-based PET/CT reduces the minimum detectable activity of iodine-124.

The radioiodine isotope pair 124I/131I is used in a theranostic approach for patient-specific treatment of differentiated thyroid cancer. Lesion detectability is notably higher for 124I PET (positron emission tomography) than for 131I gamma camera imaging but can be limited for small and low uptake lesions. The recently introduced silicon-photomultiplier-based (SiPM-based) PET/CT (computed tomography) systems outperform previous-generation systems in detector sensitivity, coincidence time resolution, and spatial resolution. Hence, SiPM-based PET/CT shows an improved detectability, particularly for small lesions. In this study, we compare the size-dependant minimum detectable 124I activity (MDA) between the SiPM-based Biograph Vision and the previous-generation Biograph mCT PET/CT systems and we attempt to predict the response to 131I radioiodine therapy of lesions additionally identified on the SiPM-based system. A tumour phantom mimicking challenging conditions (derived from published patient data) was used; i.e., 6 small spheres (diameter of 3.7-9.7 mm), 9 low activity concentrations (0.25-25 kBq/mL), and a very low signal-to-background ratio (20:1). List-mode emission data (single-bed position) were divided into frames of 4, 8, 16, and 30 min. Images were reconstructed with ordinary Poisson ordered-subsets expectation maximization (OSEM), additional time-of-flight (OSEM-TOF) or TOF and point spread function modelling (OSEM-TOF+PSF). The signal-to-noise ratio and the MDA were determined. Absorbed dose estimations were performed to assess possible treatment response to high-activity 131I radioiodine therapy. The signal-to-noise ratio and the MDA were improved from the mCT to the Vision, from OSEM to OSEM-TOF and from OSEM-TOF to OSEM-TOF+PSF reconstructed images, and from shorter to longer emission times. The overall mean MDA ratio of the Vision to the mCT was 0.52 ± 0.18. The absorbed dose estimations indicate that lesions ≥ 6.5 mm with expected response to radioiodine therapy would be detectable on both systems at 4-min emission time. Additional smaller lesions of therapeutic relevance could be detected when using a SiPM-based PET system at clinically reasonable emission times. This study demonstrates that additional lesions with predicted response to 131I radioiodine therapy can be detected. Further clinical evaluation is warranted to evaluate if negative 124I PET scans on a SiPM-based system can be sufficient to preclude patients from blind radioiodine therapy.

Enzalutamide Enhances PSMA Expression of PSMA-Low Prostate Cancer.

Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) prolongs overall survival in men with metastatic castration-resistant prostate cancer (mCRPC). However, men with low PSMA expression are excluded from RLT. We explored the effect of androgen receptor blockade with enzalutamide on PSMA expression. Assessment of PSMA and androgen receptor (AR) expression on the human PC cell lines 22Rv1, C4-2, and LNCaP by immunohistochemistry and flow cytometry revealed low (22Rv1) and high (C4-2 and LNCaP) PSMA expression, and high, comparable AR positivity. Treatment with enzalutamide increased PSMA levels in 22Rv1, C4-2, and LNCaP (2.2/2.3/2.6-fold, p = 0.0005/0.03/0.046) after one week compared to DMSO-treated controls as assessed by flow cytometry. NOD/Scid mice bearing 22Rv1 tumors were treated with enzalutamide for two weeks. Positron emission tomography/computed tomography (PET/CT) demonstrated higher tumor uptake of 68Ga-PSMA after enzalutamide treatment (p = 0.004). Similarly, a clinical case with low baseline PSMA avidity demonstrated increased uptake of 68Ga-PSMA after enzalutamide on PET/CT and post-therapeutic 177Lu-PSMA scintigraphy in a patient with mCRPC. Enzalutamide induced PSMA expression in the 22Rv1 xenograft model and in an mCRPC patient, both with low baseline tumoral PSMA levels. Therefore, enzalutamide pre-treatment might render patients with low PSMA expression eligible for 177Lu-PSMA RLT.

Estimating the modulating effect of lung tissue in particle therapy using a clinical CT voxel histogram analysis.

To treat lung tumours with particle therapy, different additional tasks and challenges in treatment planning and application have to be addressed thoroughly. One of these tasks is the quantification and consideration of the Bragg peak (BP) degradation due to lung tissue: as lung is an heterogeneous tissue, the BP is broadened when particles traverse the microscopic alveoli. These are not fully resolved in clinical CT images and thus, the effect is not considered in the dose calculation. In this work, a correlation between the CT histograms of heterogeneous material and the impact on the BP curve is presented. Different inorganic materials were scanned with a conventional CT scanner and additionally, the BP degradation was measured in a proton beam and was then quantified. A model is proposed that allows an estimation of the modulation power by performing a histogram analysis on the CT scan. To validate the model for organic samples, a second measurement series was performed with frozen porcine lunge samples. This allows to investigate the possible limits of the proposed model in a set-up closer to clinical conditions. For lung substitutes, the agreement between model and measurement is within ±0.05 mm and for the organic lung samples, within ±0.15 mm. This work presents a novel, simple and efficient method to estimate if and how much a material or a distinct region (within the lung) is degrading the BP on the basis of a common clinical CT image. Up until now, only a direct in-beam measurement of the region or material of interest could answer this question.

Beta radioguided surgery: towards routine implementation?

In locally or locally advanced solid tumors, surgery still remains a fundamental treatment method. However, conservative resection is associated with high collateral damage and functional limitations of the patient. Furthermore, the presence of residual tumor tissue following conservative surgical treatment is currently a common cause of locally recurrent cancer or of distant metastases. Reliable intraoperative detection of small cancerous tissue would allow surgeons to selectively resect malignant areas: this task can be achieved by means of image-guided surgery, such as beta radioguided surgery (RGS). In this paper, a comprehensive review of beta RGS is given, starting from the physical principles that differentiate beta from gamma radiation, that already has its place in current surgical practice. Also, the recent clinical feasibility of using Cerenkov radiation is discussed. Despite being first proposed several decades ago, only in the last years a remarkable interest in beta RGS has been observed, probably driven by the diffusion of PET radiotracers. Today several different approaches are being pursued to assess the effectiveness of such a technique, including both beta+ and beta- emitting radiopharmaceuticals. Beta RGS shows some peculiarities that can present it as a very promising complementary technique to standard procedures. Good results are being obtained in several tests, both ex vivo and in vivo. This might however be the time to initiate the trials to demonstrate the real clinical value of these technologies with seemingly clear potential.

Evaluation of [68Ga]Ga-PSMA PET/CT images acquired with a reduced scan time duration in prostate cancer patients using the digital biograph vision.

AIM: [68Ga]Ga-PSMA-11 PET/CT allows for a superior detection of prostate cancer tissue, especially in the context of a low tumor burden. Digital PET/CT bears the potential of reducing scan time duration/administered tracer activity due to, for instance, its higher sensitivity and improved time coincidence resolution. It might thereby expand [68Ga]Ga-PSMA-11 PET/CT that is currently limited by 68Ge/68Ga-generator yield. Our aim was to clinically evaluate the influence of a reduced scan time duration in combination with different image reconstruction algorithms on the diagnostic performance. METHODS: Twenty prostate cancer patients (11 for biochemical recurrence, 5 for initial staging, 4 for metastatic disease) sequentially underwent [68Ga]Ga-PSMA-11 PET/CT on a digital Siemens Biograph Vision. PET data were collected in continuous-bed-motion mode with a mean scan time duration of 16.7 min (reference acquisition protocol) and 4.6 min (reduced acquisition protocol). Four iterative reconstruction algorithms were applied using a time-of-flight (TOF) approach alone or combined with point-spread-function (PSF) correction, each with 2 or 4 iterations. To evaluate the diagnostic performance, the following metrics were chosen: (a) per-region detectability, (b) the tumor maximum and peak standardized uptake values (SUVmax and SUVpeak), and (c) image noise using the liver's activity distribution. RESULTS: Overall, 98% of regions (91% of affected regions) were correctly classified in the reduced acquisition protocol independent of the image reconstruction algorithm. Two nodal lesions (each ≤ 4 mm) were not identified (leading to downstaging in 1/20 cases). Mean absolute percentage deviation of SUVmax (SUVpeak) was approximately 9% (6%) for each reconstruction algorithm. The mean image noise increased from 13 to 21% (4 iterations) and from 10 to 15% (2 iterations) for PSF + TOF and TOF images. CONCLUSIONS: High agreement at 3.5-fold reduction of scan time in terms of per-region detection (98% of regions) and image quantification (mean deviation ≤ 10%) was demonstrated; however, small lesions can be missed in about 10% of patients leading to downstaging (T1N0M0 instead of T1N1M0) in 5% of patients. Our results suggest that a reduction of scan time duration or administered [68Ga]Ga-PSMA-11 activities can be considered in metastatic patients, where missing small lesions would not impact patient management. Limitations include the small and heterogeneous sample size and the lack of follow-up.