Tomography Tracer Research Articles

Chemokine Receptor 2 Targeted PET/CT Imaging Distant Metastases in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and treatment-refractory malignancies. The lack of an effective screening tool results in the majority of patients being diagnosed at late stages, which underscores the urgent need to develop more sensitive and specific imaging modalities, particularly in detecting occult metastases, to aid clinical decision-making. The tumor microenvironment of PDAC is heavily infiltrated with myeloid-derived suppressor cells (MDSCs) that express C-C chemokine receptor type 2 (CCR2). These CCR2-expressing MDSCs accumulate at a very early stage of metastasis and greatly outnumber PDAC cells, making CCR2 a promising target for detecting early, small metastatic lesions that have scant PDAC cells. Herein, we evaluated a CCR2 targeting PET tracer (68Ga-DOTA-ECL1i) for PET imaging on PDAC metastasis in two mouse models. Positron emission tomography/computed tomography (PET/CT) imaging of 68Ga-DOTA-ECL1i was performed in a hemisplenic injection metastasis model (KI) and a genetically engineered orthotopic PDAC model (KPC), which were compared with 18F-FDG PET concurrently. Autoradiography, hematoxylin and eosin (H&E), and CCR2 immunohistochemical staining were performed to characterize the metastatic lesions. PET/CT images visualized the PDAC metastases in the liver/lung of KI mice and in the liver of KPC mice. Quantitative uptake analysis revealed increased metastasis uptake during disease progression in both models. In comparison, 18F-FDG PET failed to detect any metastases during the time course studies. H&E staining showed metastases in the liver and lung of KI mice, within which immunostaining clearly demonstrated the overexpression of CCR2 as well as CCR2+ cell infiltration into the normal liver. H&E staining, CCR2 staining, and autoradiography also confirmed the expression of CCR2 and the uptake of 68Ga-DOTA-ECL1i in the metastatic foci in KPC mice. Using our novel CCR2 targeted radiotracer 68Ga-DOTA-ECL1i and PET/CT, we demonstrated the sensitive and specific detection of CCR2 in the early PDAC metastases in two mouse models, indicating its potential in future clinical translation.

Evaluation of Chelator-to-Antibody Ratio on Development of 89Zr-iPET Tracer for Imaging of PD-L1 Expression on Tumor.

89Zr-iPET has been widely used for preclinical and clinical immunotherapy studies to predict patient stratification or evaluate therapeutic efficacy. In this study, we prepared and evaluated 89Zr-DFO-anti-PD-L1-mAb tracers with varying chelator-to-antibody ratios (CARs), including 89Zr-DFO-anti-PD-L1-mAb_3X (tracer_3X), 89Zr-DFO-anti-PD-L1-mAb_10X (tracer_10X), and 89Zr-DFO-anti-PD-L1-mAb_20X (tracer_20X). The DFO-anti-PD-L1-mAb conjugates with varying CARs were prepared using a random conjugation method and then subjected to quality control. The conjugates were radiolabeled with 89Zr and evaluated in a PD-L1-expressing CT26 tumor-bearing mouse model. Next, iPET imaging, biodistribution, pharmacokinetics, and ex vivo pathological and immunohistochemical examinations were conducted. LC-MS analysis revealed that DFO-anti-PD-L1-mAb conjugates were prepared with CARs ranging from 0.4 to 2.0. Radiochemical purity for all tracer groups was >99% after purification. The specific activity levels of tracer_3X, tracer_10X, and tracer_20X were 2.2 ± 0.6, 8.2 ± 0.6, and 10.5 ± 1.6 μCi/μg, respectively. 89Zr-iPET imaging showed evident tumor uptake in all tracer groups and reached the maximum uptake value at 24 h postinjection (p.i.). Biodistribution data at 168 h p.i. revealed that the tumor-to-liver, tumor-to-muscle, and tumor-to-blood uptake ratios for tracer_3X, tracer_10X, and tracer_20X were 0.46 ± 0.14, 0.58 ± 0.33, and 1.54 ± 0.51; 4.7 ± 1.3, 7.1 ± 3.9, and 14.7 ± 1.1; and 13.1 ± 5.8, 19.4 ± 13.8, and 41.3 ± 10.6, respectively. Significant differences were observed between tracer_3X and tracer_20X in the aforementioned uptake ratios at 168 h p.i. The mean residence time and elimination half-life for tracer_3X, tracer_10X, and tracer_20X were 25.4 ± 4.9, 24.2 ± 6.1, and 25.8 ± 3.3 h and 11.8 ± 0.5, 11.1 ± 0.7, and 11.7 ± 0.6 h, respectively. No statistical differences were found between-tracer in the aforementioned pharmacokinetic parameters. In conclusion, 89Zr-DFO-anti-PD-L1-mAb tracers with a CAR of 1.4-2.0 may be better at imaging PD-L1 expression in tumors than are traditional low-CAR 89Zr-iPET tracers.

Radiopharmaceutical selection for tau PET imaging

AbstractBackgroundThe accumulation of pathologically misfolded tau is a feature that is shared by a group of neurodegenerative disorders that are collectively referred to as tauopathies. AD is the most prevalent of these tauopathies. Neurofibrillary tangles are characterized by the presence of hyperphosphorylated protein (tau), and senile plaques are characterized by the presence of amyloid peptide aggregates. PET imaging is fully quantitative and enables accurate spatial assessment. However, as a result of non‐specific binding and the limited spatial resolution of PET scanners, this technique requires not only the presence of tau inclusions in a brain region but also sufficient density and spatial extent of those inclusions in order to generate a sufficient signal‐to‐noise ratio. With the development of tau‐specific ligands for use with PET, it is now possible to investigate the role that tau pathology plays in the development and progression of these disorders. The purpose of this study is to analyze, compare, and rank the currently available tau PET tracers for imaging in research and routine clinical settings.MethodWe proposed using the fuzzy Preference Ranking Organization Method for Enrichment of Evaluations (PROMETHEE), a multicriteria decision‐making (MCDM) tool. First‐generation tau PET tracers ([18F]AV1451, [11C]PBB3, [18F]THK5117, [18F]THK5351, [18F]THK5317, and [18F]THK5105) and second‐generation compounds ([18F]MK‐6240, [18F]JNJ‐067, [18F] PI‐2620, [18F]RO‐948 (previously referred to as [18F]RO69558948), [18F]PM‐PBB3, [18F]GTP1, [18F]JNJ‐64349311 ([18F]JNJ311), [11C]RO‐6931643, and [11C]RO‐6924963) were selected to investigate in this study. The evaluation is based on relative parameters, such as specificity, target binding accuracy, neocortical uptake, radiation exposure, brain penetration, free fraction in plasma, defluorination, and adverse reactions, and the importance that is placed on each of these parameters is weighted differently.ResultThe results from this study show that [18F]RO‐948 is the most favorable tau PET ligand, while[18F]THK5105 is the least favorable one based on the considered weighted criteria in this study.ConclusionFuzzy PROMETHEE can be used as a decision‐aid system to select the proper radiopharmaceuticals for tau PET imaging. This study can be extended to include more tracers and criteria and might help researchers and concerned readers to select the optimal tau PET tracer.

Abstract A068: Site-specific modification of nanobodies for ImmunoPET of Liver Cancer utilizing Self-labeling nanobody-tag pair (SLANT) technology

Abstract Visualization of tumor cells is critical in diagnosing, monitoring, and treating patients with cancer. Liver cancer has an 18 percent 5-year survival rate and is the third leading cause of cancer-related deaths worldwide. Hepatocellular carcinoma (HCC), the most common type of liver cancer, only takes up 18F-fluorodeoxyglucose (18F-FDG), the most commonly used clinical positron emission tomography (PET) tracer, 50% of the time. As such, developing an HCC-selective imaging agent could improve our ability for earlier diagnosis, post-treatment surveillance, and ability to increase patient longevity and quality of life. Single domain antibodies (sdAbs), or nanobodies (Nb), are attractive scaffolds for radiopharmaceutical development because of their high target affinity and specificity, ready availability from recombinant expression in bacteria, and small size for rapid clearance, better tumor penetration, and same-day imaging. However, conventional conjugation chemistry that exploits cysteines or lysines found on the native protein can abrogate the binding site of the smaller Nbs. We have previously used sortase A-based site-specific conjugation to address these challenges; however, improvements were still possible. Here, we developed a novel self-labeling Nb-tag pair (SLANT) that allows fast and specific covalent labeling of a Nb based on peptide epitope binding. We used SLANT to engineer a heterodimeric Nb construct consisting of a Nb (HN3) specific for Glypican-3, a heparin sulfate proteoglycan that is overexpressed in 75-90% of all HCCs and our self-labeling Nb. This design allows for site-specific labeling of the heterodimeric (GPC3-specific) construct in a manner that avoids modification of the tumor antigen-specific protomer. Labeling is achieved via exposure of the fusion protein to a crosslinking peptide functionalized with a chelator (DOTA). This methodology produces labeled protein at over 90 percent yields within minutes compared to less than 30 percent yields utilizing enzymatic methods. Biolayer interferometry and radioligand saturation studies were done to determine the binding affinity of the conjugate for GPC3 pre- and post-Indium-111 labeling. SPECT/CT and biodistribution studies were done at 1h, 3hrs, and 24hrs with HepG2 and HepG2-GPC3- xenografts to assess conjugate specificity and ability to accumulate in GPC3+ liver tumors. Our conjugate exhibited a nanomolar affinity for GPC3 in vitro (17-36 nM). SPECT/CT and biodistribution studies showed specificity for GPC3 in HepG2 liver cancer xenografts (~5.5% IA/g at 1-hour post-injection (p.i.)) and minimal uptake in HepG2 GPC3- tumors (~0.62% IA/g at 1-hour p.i.). Our results highlight the development of a new labeling paradigm applied to GPC3+ liver cancer. This approach can be used for same-day imaging and the rapid development of SPECT and PET imaging tracers for different cellular markers on cancer cells, addressing known tumor heterogeneity. Citation Format: Stanley Fayn, Chino C Cabalteja, Woonghee Lee, Divya Nambiar, Kwamena E Baidoo, Freddy E Escorcia, Ross W Cheloha. Site-specific modification of nanobodies for ImmunoPET of Liver Cancer utilizing Self-labeling nanobody-tag pair (SLANT) technology [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A068.

Three-dimensional X-ray imaging of macropore flow

Macropores are known to be important pathways for the rapid transport of water, solutes and colloids in soil. Nevertheless, we still know very little about how the topology and geometry of macropore networks govern water flow configurations and velocities in natural soil. In this study, we aimed at gaining more insight into macropore flow by using X-ray tomography to quantify air–water distributions in the macropore networks of undisturbed topsoil and subsoil columns of a clay soil at varying steady-state flow rates. We observed that while large fractions of the macropore network remained air-filled, the air phase only became entrapped when the irrigation rate was very close to the saturated hydraulic conductivity of the soil. The data enabled us to parameterize a kinematic wave model for water flow following the approach proposed in Jarvis et al. (2017a). Follow-up experiments would be required to evaluate whether these kinematic wave parameters derived by X-ray imaging match with those obtained from outflow measurements. We found that quantitative X-ray imaging of macropore flow through soils still remains a challenging task. We recommend that future experiments are conducted on smaller soil samples to improve image resolution and minimize experimental time spans as well as X-ray image noise and illumination bias. Such experiments could also include 3-D tracer imaging to identify the imaged macropore networks transporting most of the water (i.e. the backbone) at varying steady irrigation rates.

First magnetic particle imaging to assess pulmonary vascular leakage in vivo in the acutely injured and fibrotic lung.

Increased pulmonary vascular permeability is a characteristic feature of lung injury. However, there are no established methods that allow the three-dimensional visualization and quantification of pulmonary vascular permeability in vivo. Evans blue extravasation test and total protein test of bronchoalveolar lavage fluid (BALF) are permeability assays commonly used in research settings. However, they lack the ability to identify the spatial and temporal heterogeneity of endothelial barrier disruption, which is typical in lung injuries. Magnetic resonance (MR) and near-infrared (NIR) imaging have been proposed to image pulmonary permeability, but suffer from limited sensitivity and penetration depth, respectively. In this study, we report the first use of magnetic particle imaging (MPI) to assess pulmonary vascular leakage noninvasively in vivo in mice. A dextran-coated superparamagnetic iron oxide (SPIO), synomag®, was employed as the imaging tracer, and pulmonary SPIO extravasation was imaged and quantified to evaluate the vascular leakage. Animal models of acute lung injury and pulmonary fibrosis (PF) were used to validate the proposed method. MPI sensitively detected the SPIO extravasation in both acutely injured and fibrotic lungs in vivo, which was confirmed by ex vivo imaging and Prussian blue staining. Moreover, 3D MPI illustrated the spatial heterogeneity of vascular leakage, which correlated well with CT findings. Based on the in vivo 3D MPI images, we defined the SPIO extravasation index (SEI) to quantify the vascular leakage. A significant increase in SEI was observed in the injured lungs, in consistent with the results obtained via ex vivo permeability assays. Overall, our results demonstrate that 3D quantitative MPI serves as a useful tool to examine pulmonary vascular integrity in vivo, which shows promise for future clinical translation.

Investigation of the Uniformity of Gel Shrinkage by Imaging Tracer Particles Using X‐Ray Microtomography

Mass transfer and structural changes in the polymer matrix need to be understood for a rational optimization of the biopolymer‐based aerogels production. Herein, the uniformity of changes that occur in the gel structure during the aerogel production by a newly developed method which is based on the imaging of metal tracer particles using X‐ray microtomography (X‐ray micro‐CT) alongside the application of point pattern techniques such as the K‐nearest‐neighbor (KNN) distances is studied. Agar is initially used as a system of validation for the developed method, after which other polysaccharide and protein‐based gels such as alginate, whey protein isolate (WPI), and gelatine are studied. The KNN distance is seen to reduce from hydrogel to aerogel. Furthermore, by means of the KNN distances, the biopolymers are observed to experience a nonuniform distribution of tracer particles correlating to nonuniform shrinkage. Densification at specific sites of the gel represented by lower KNN distance values could be distinguished for each biopolymer. Finally, the spatially resolved polymer network density profile is estimated from the KNN distance by correlating it to experimentally determined polymer network density.

Synthesis and preclinical evaluation of novel 18F-labeled fibroblast activation protein tracers for positron emission tomography imaging of cancer-associated fibroblasts

Fibroblast activation protein (FAP) is overexpressed in cancer-associated fibroblasts in more than 90% of epithelial tumors. Several radiotracers targeting FAPs have been used in clinical settings in recent years. However, the number of 18F-labeled FAP tracers is still limited. Herein, we aimed to develop 18F-labeled FAP tracers with optimized pharmacokinetics. Labeling precursors (NOTA-DD-FAPI and NOTA-PD-FAPI) were synthesized and labeled with fluorine‐18. The precursors NOTA-DD-FAPI (IC50 = 0.21 ± 0.06 nM) and NOTA -PD-FAPI (IC50 = 0.13 ± 0.07 nM) showed a higher affinity for FAP compared to NOTA-FAPI-42 (IC50 = 0.66 ± 0.19 nM). Novel 18F-labeled FAP tracers showed a specific uptake, high internalized fraction, and low cellular efflux in vitro. Compared to the clinically used tracer [18F]AlF-FAPI-42, both the novel 18F-labeled FAP tracers, and especially the [18F]AlF-PD-FAPI tracer with a higher tumor-to-background ratio demonstrated rapid renal excretion and higher tumor uptake during preclinical evaluation, resulting in images with higher contrast. Thus, [18F]AlF-PD-FAPI shows promise for use as a FAP-targeting tracer for clinical translation.

Cryo-EM of Aβ fibrils from mouse models find tg-APPArcSwe fibrils resemble those found in patients with sporadic Alzheimer’s disease

The use of transgenic mice displaying amyloid-β (Aβ) brain pathology has been essential for the preclinical assessment of new treatment strategies for Alzheimer’s disease. However, the properties of Aβ in such mice have not been systematically compared to Aβ in the brains of patients with Alzheimer’s disease. Here, we determined the structures of nine ex vivo Aβ fibrils from six different mouse models by cryogenic-electron microscopy. We found novel Aβ fibril structures in the APP/PS1, ARTE10 and tg-SwDI models, whereas the human type II filament fold was found in the ARTE10, tg-APPSwe and APP23 models. The tg-APPArcSwe mice showed an Aβ fibril whose structure resembles the human type I filament found in patients with sporadic Alzheimer’s disease. A detailed assessment of the Aβ fibril structure is key to the selection of adequate mouse models for the preclinical development of novel plaque-targeting therapeutics and positron emission tomography imaging tracers in Alzheimer’s disease.

The second phase-3 multi-center trial of flurpiridaz F-18 PET myocardial perfusion imaging for coronary artery disease evaluation

Abstract Background/Introduction Flurpiridaz F-18 (flurpiridaz) is a novel PET myocardial perfusion imaging tracer with outstanding imaging characteristics. Purpose To further assess the diagnostic efficacy and safety of flurpiridaz PET for the detection and evaluation of coronary artery disease (CAD) defined as >50% stenosis by quantitative invasive coronary angiography (ICA) in a multi-center prospective international clinical trial. The primary end point was to assess the diagnostic efficacy (sensitivity and specificity) of flurpiridaz PET MPI for the detection of CAD. The secondary end points were to compare the diagnostic performance of flurpiridaz PET vs. Tc-99m SPECT in the detection of CAD in all patients and in the clinically important subgroups of women, obese [body mass index (BMI) ≥30 kg/m2], and diabetics. Also, PET and Tc-99m SPECT were compared for defect severity/extent, image quality, confidence of interpretation and radiation dose to patients. The safety of flurpiridaz PET was also evaluated. Methods 730 patients with suspected CAD from 48 clinical sites in US, Canada and Europe were enrolled. Patients underwent 1-day rest/stress (pharmacological or exercise) flurpiridaz PET and 1- or 2-day rest-stress Tc-99m labeled SPECT before ICA. PET and SPECT images were read by 3 experts blinded to clinical and ICA data. ICA was quantified by a core laboratory expert blinded to clinical and image data. Results 578 patients (age, 63.7±9.5 years) were evaluable. Flurpiridaz PET met the prespecified primary endpoint of the study; sensitivity and specificity were significantly higher than the prespecified threshold value by two of the three readers. The secondary endpoints were also met in the overall population, in women, in obese patients, and in diabetics. Flurpiridaz PET ROC area under the curves were significantly higher than SPECT in the overall population (0.80 vs 0.68, p<0.0001), in women (0.84 vs 0.70, p<0.01), and in obese patients (0.79 vs 0.67, p<0.001), but not in diabetics (0.76 vs 0.69, p=0.088). Flurpiridaz PET was also superior to SPECT for assessment of defect extent/severity (p<0.0001). Image quality (% excellent or good) of flurpiridaz PET was significantly better than SPECT for rest images (93% vs 72%, p<0.0001), pharmacological stress images (96% vs 78%, p<0.0001), and treadmill exercise images (97% vs 87%, p<0.05). Radiation exposure, evaluated in 604 dosed patients, was less for PET than same-day rest/stress SPECT using either Tetrofosmin or Sestamibi with 6.25 mSv for flurpiridaz PET, 9.86 mSv for 99mTc-tetrofosmin SPECT and 12.41 mSv for 99mTc-sestamibi SPECT. Conclusion This second flurpiridaz PET myocardial perfusion imaging multicenter international trial demonstrates that flurpiridaz has promise as a new tracer for detection and evaluation of coronary artery disease. This is particularly so in women and patients with BMI≥30.

Abstract 12853: [ 64 Cu]Cu-DOTATATE is Superior to [ 68 Ga]Ga-NODAGA-E[c(RGDyK)]2 (RGD) PET/CT Imaging In Detection and Quantification of Atherosclerosis: A Retrospective Analysis of a Phase 2 Trial Cohort

Introduction: Inflammation and angiogenesis are central to development of atherosclerosis. [ 64 Cu]Cu-DOTATATE and [ 68 Ga]Ga-NODAGA-E[c(RGDyK)]2 (RGD) are PET tracers that can non-invasively visualize somatostatin receptor subtype 2 (SSTR 2 ) and α v β 3 integrin expression that represent inflammation and angiogenesis respectively. Hypothesis: Whether an imaging tracer of inflammation can be compared with a tracer of angiogenesis for detection and quantification of the atherosclerotic process in patients from a Phase II cancer trial cohort. Methods: A cohort of patients from Phase II trial were divided in three groups as controls (N=7), at risk (N=6) & diseased (N=7). PET/CT scans with two different tracers were performed in all subjects. The scans were retrospectively analyzed, and tracer uptake (mean of maximum target-to-background ratios (mTBRmax)) were determined in 6 arterial segments. In addition, plaques from patients (N=7) undergoing carotid endarterectomy (CEA) were studied with autoradiography and immunohistochemistry. Results: [ 64 Cu]Cu-DOTATATE uptake in the disease group was significantly higher compared to the control group in the abdominal aorta (4.4 vs 2.1, p=0.02), thoracic aorta (3.0 vs 2.2, p=0.02), aortic arch (2.8 vs 2.2, p=0.03), left carotid artery (2.2 vs 1.3, p=0.02) and the average of all six aortic segments (2.7 vs 2.0, p=0.01) whereas all aortic segments in the disease group showed a higher but a non-significant difference compared to the control group with RGD uptake. A moderate correlation was found between the mean aortic uptake of [ 64 Cu]Cu-DOTATATE & RGD (r=0.41, p=0.01) in patients from the disease group. SSTR 2 and α v β 3 expression was confirmed on ex vivo plaques along with tracer binding. Conclusions: An in vivo imaging marker of inflammation was superior to a marker of angiogenesis in discriminating levels of atherosclerosis. The two markers were weakly correlated in patients with known cardiovascular disease.

P-027 - Radiosynthesis and Evaluation of a Novel 18F-Labeled Tracer for PET Imaging of Glycogen Synthase Kinase-3 (GSK-3)

P-027 - Radiosynthesis and Evaluation of a Novel 18F-Labeled Tracer for PET Imaging of Glycogen Synthase Kinase-3 (GSK-3)

P-119 - Synthesis and Preclinical Evaluation of Three Novel 68Ga-labeled PSMA-FAP Heterodimeric Tracers for Imaging of Prostate Cancer

P-119 - Synthesis and Preclinical Evaluation of Three Novel 68Ga-labeled PSMA-FAP Heterodimeric Tracers for Imaging of Prostate Cancer

P-142 - In vivo evaluation of [18F]Fluoroethyl Fucose: a PET tracer for imaging and studying tumor senescence

P-142 - In vivo evaluation of [18F]Fluoroethyl Fucose: a PET tracer for imaging and studying tumor senescence

P-024 - Comparison of [11C] and [18F] labelled D-amino acid tracers for imaging of bacterial infection

P-024 - Comparison of [11C] and [18F] labelled D-amino acid tracers for imaging of bacterial infection

P-210 - Synthesis of a carbon-11 labeled imidazo[1,2-a]pyridine derivative as a new potential PET tracer for imaging of PI3K/mTOR in cancer

P-210 - Synthesis of a carbon-11 labeled imidazo[1,2-a]pyridine derivative as a new potential PET tracer for imaging of PI3K/mTOR in cancer

P-214 - Radiosynthesis and evaluation of a new PET tracer for imaging of leucine-rich repeat kinase 2

P-214 - Radiosynthesis and evaluation of a new PET tracer for imaging of leucine-rich repeat kinase 2

O-59 - Preclinical evaluation of [89Zr]Zr-DFO*-sacituzumab, a PET tracer for imaging of whole body TROP-2 expression as a potential selection tool for treatment with TROP-2 antibody drug conjugates (ADC)

O-59 - Preclinical evaluation of [89Zr]Zr-DFO*-sacituzumab, a PET tracer for imaging of whole body TROP-2 expression as a potential selection tool for treatment with TROP-2 antibody drug conjugates (ADC)

P-103 - F-18 labeled azaindole derivatives as PET imaging tracer for tau protein

P-103 - F-18 labeled azaindole derivatives as PET imaging tracer for tau protein

Comparison of PET/CT-based eligibility according to VISION and TheraP trial criteria in end-stage prostate cancer patients undergoing radioligand therapy.

Two randomized clinical trials demonstrated the efficacy of prostate-specific membrane antigen (PSMA) radioligand therapy (PSMA RLT) in metastatic castration-resistant prostate cancer (mCRPC). While the VISION trial used criteria within PSMA PET/CT for inclusion, the TheraP trial used dual tracer imaging including FDG PET/CT. Therefore, we investigated whether the application of the VISION criteria leads to a benefit in overall survival (OS) or progression-free survival (PFS) for men with mCRPC after PSMA RLT. Thirty-five men with mCRPC who had received PSMA RLT as a last-line option and who had undergone pretherapeutic imaging with FDG and [68Ga]Ga-PSMA I&T or [18F]PSMA-1007 were studied. Therapeutic eligibility was retrospectively evaluated using the VISION and TheraP study criteria. 26 of 35 (74%) treated patients fulfilled the VISION criteria (= VISION+) and only 17 of 35 (49%) fulfilled the TheraP criteria (= TheraP+). Significantly reduced OS and PFS after PSMA RLT was observed in patients rated VISION- compared to VISION+ (OS: VISION-: 3 vs. VISION+: 12months, hazard ratio (HR) 3.1, 95% confidence interval (CI) 1.0-9.1, p < 0.01; PFS: VISION-: 1 vs. VISION+: 5months, HR 2.7, 95% CI 1.0-7.8, p < 0.01). For patients rated TheraP-, no significant difference in OS but in PFS was observed compared to TheraP+ patients (OS: TheraP-: 5.5 vs. TheraP+: 11months, HR 1.6, 95% CI 0.8-3.3, p = 0.2; PFS: TheraP-: 1 vs. TheraP+: 6months, HR 2.2, 95% CI 1.0-4.5, p < 0.01). Retrospective application of the inclusion criteria of the VISION study leads to a benefit in OS and PFS after PSMA RL, whereas TheraP criteria appear to be too strict in patients with end-stage prostate cancer. Thus, performing PSMA PET/CT including a contrast-enhanced CT as proposed in the VISION trial might be sufficient for treatment eligibility of end-stage prostate cancer patients.