Relapsing Polychondritis with Tracheobronchial Involvement: A Detailed Description of Two Pediatric Cases and Review of the Literature.

Relapsing polychondritis (RP) is a rare immune-mediated disease that primarily affects the cartilaginous structures of the ears, nose and airways. The clinical spectrum ranges from mild to severe disease characterized by progressive destruction of cartilage in the tracheobronchial tree leading to airway obstruction and acute respiratory failure. Early diagnosis is crucial to prevent irreversible airway damage and life-threatening complications. Due to its rarity and variability of symptoms, the diagnosis of RP is often delayed particularly in childhood. To address this and increase awareness of this rare disease, we present a detailed case report of two adolescent females affected by RP. We aim to describe the clinical findings, consequences of a delayed diagnosis and provide a review of the current literature.

Mycophenolate mofetil in giant cell arteritis.

Introduction: Giant cell arteritis (GCA) is a systemic granulomatous vasculitis affecting the large arteries. Abnormal lymphocyte function has been noted as a pathogenic factor in GCA. Mycophenolate mofetil (MMF) inhibits inosine monophosphate dehydrogenase and is therefore a highly lymphocyte-specific immunosuppressive therapy. We aimed to assess the efficacy of MMF for inducing remission in GCA. Methods: Seven patients (5 female, 2 male) with GCA under therapy with MMF and who were treated at the outpatient clinic for rare inflammatory systemic diseases at Hannover Medical School between 2010 and 2023 were retrospectively included in the study. All patients underwent duplex sonography, 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET), magnetic resonance imaging (MRI), and/or biopsy to confirm the diagnosis. The primary endpoints were the number of recurrences, CRP levels at 3-6 and 6-12 months, and the period of remission. Results: All patients in this case series showed inflammatory activity of the arterial vessels in at least one of the imaging modalities: duplex sonography (n = 5), 18F-FDG PET (n = 5), MRI (n = 6), and/or biopsy (n = 5). CRP levels of all patients decreased at the measurement time points 3-6 months, and 6-9 months after initiation of therapy with MMF compared with CRP levels before MMF therapy. All patients with GCA in this case series achieved disease remission. Discussion: The results of the present case series indicate that MMF is an effective therapy in controlling disease activity in GCA, which should be investigated in future randomized controlled trials.

Interplay between driveline infection, vessel wall inflammation, cerebrovascular events and mortality in patients with left ventricular assist device.

In patients with left ventricular assist device (LVAD), infections and thrombotic events represent severe complications. We investigated device-specific local and systemic inflammation and its impact on cerebrovascular events (CVE) and mortality. In 118 LVAD patients referred for 18F-FDG-PET/CT, metabolic activity of LVAD components, thoracic aortic wall, lymphoid and hematopoietic organs, was quantified and correlated with clinical characteristics, laboratory findings, and outcome. Driveline infection was detected in 92/118 (78%) patients by 18F-FDG-PET/CT. Activity at the driveline entry site was associated with increased signals in aortic wall (r = 0.32, p < 0.001), spleen (r = 0.20, p = 0.03) and bone marrow (r = 0.20, p = 0.03), indicating systemic interactions. Multivariable analysis revealed independent associations of aortic wall activity with activity of spleen (ß = 0.43, 95% CI 0.18-0.68, p < 0.001) and driveline entry site (ß = 0.04, 95% CI 0.01-0.06, p = 0.001). Twenty-two (19%) patients suffered CVE after PET/CT. In a binary logistic regression analysis metabolic activity at the driveline entry site missed the level of significance as an influencing factor for CVE after adjusting for anticoagulation (OR = 1.16, 95% CI 1-1.33, p = 0.05). Metabolic activity of the subcutaneous driveline (OR = 1.13, 95% CI 1.02-1.24, p = 0.016) emerged as independent risk factor for mortality. Molecular imaging revealed systemic inflammatory interplay between thoracic aorta, hematopoietic organs, and infected device components in LVAD patients, the latter predicting CVE and mortality.

Prostate-specific Membrane Antigen Reporting and Data System Version 2.0.

Prostate-specific Membrane Antigen Reporting and Data System (PSMA-RADS) was introduced for standardized reporting, and PSMA-RADS version 1.0 allows classification of lesions based on their likelihood of representing a site of prostate cancer on PSMA-targeted positron emission tomography (PET). In recent years, this system has extensively been investigated. Increasing evidence has accumulated that the different categories reflect their actual meanings, such as true positivity in PSMA-RADS 4 and 5 lesions. Interobserver agreement studies demonstrated high concordance among a broad spectrum of 68Ga- or 18F-labeled, PSMA-directed radiotracers, even for less experienced readers. Moreover, this system has also been applied to challenging clinical scenarios and to assist in clinical decision-making, for example, to avoid overtreatment in oligometastatic disease. Nonetheless, with an increasing use of PSMA-RADS 1.0, this framework has shown not only benefits, but also limitations, for example, for follow-up assessment of locally treated lesions. Thus, we aimed to update the PSMA-RADS framework to include a refined set of categories in order to optimize lesion-level characterization and best assist in clinical decision-making (PSMA-RADS version 2.0).

Molecular Imaging of Myocardial Fibroblast Activation in Patients with Advanced Aortic Stenosis Before Transcatheter Aortic Valve Replacement: A Pilot Study.

Using multimodal imaging, we investigated the extent and functional correlates of myocardial fibroblast activation in patients with aortic stenosis (AS) scheduled for transcatheter aortic valve replacement (TAVR). AS may cause myocardial fibrosis, which is associated with disease progression and may limit response to TAVR. Novel radiopharmaceuticals identify upregulation of fibroblast activation protein (FAP) as a cellular substrate of cardiac profibrotic activity. Methods: Twenty-three AS patients underwent 68Ga-FAP inhibitor 46 (68Ga-FAPI) PET, cardiac MRI, and echocardiography within 1-3 d before TAVR. Imaging parameters were correlated and then were integrated with clinical and blood biomarkers. Control cohorts of subjects without a history of cardiac disease and with (n = 5) and without (n = 9) arterial hypertension were compared with matched AS subgroups. Results: Myocardial FAP volume varied significantly among AS subjects (range, 1.54-138 cm3, mean ± SD, 42.2 ± 35.6 cm3) and was significantly higher than in controls with (7.42 ± 8.56 cm3, P = 0.007) and without (2.90 ± 6.67 cm3; P < 0.001) hypertension. FAP volume correlated with N-terminal prohormone of brain natriuretic peptide (r = 0.58, P = 0.005), left ventricular ejection fraction (r = -0.58, P = 0.02), mass (r = 0.47, P = 0.03), and global longitudinal strain (r = 0.55, P = 0.01) but not with cardiac MRI T1 (spin-lattice relaxation time) and extracellular volume (P = not statistically significant). In-hospital improvement in left ventricular ejection fraction after TAVR correlated with pre-TAVR FAP volume (r = 0.440, P = 0.035), N-terminal prohormone of brain natriuretic peptide, and strain but not with other imaging parameters. Conclusion: FAP-targeted PET identifies varying degrees of left ventricular fibroblast activation in TAVR candidates with advanced AS. 68Ga-FAPI signal does not match other imaging parameters, generating the hypothesis that it may become useful as a tool for personalized selection of optimal TAVR candidates.

[Positron emission tomography in oncology]. / Positronenemissionstomographie in der Onkologie.

Positron emission tomography (PET) is a highly sensitive imaging tool that noninvasively characterizes metabolic processes and molecular targets. PET has become an integral part of oncological diagnostics and an increasingly important tool for oncological therapy management. PET assessment, for example, directly influences treatment escalation or de-escalation in context of Hodgkin lymphomas or is, in case of lung cancer, able to reduce unnecessary surgeries. Hence, molecular PET imaging represents an indispensable tool in the development of personalized treatments. Furthermore, the development of new radiotracers for specific cell surface structures offers a promising potential for diagnostics and-combined with therapeutic nuclides-also for therapies. One recent example are radioligands targeting prostate-specific membrane antigen, which are relevant in prostate cancer.

Clinical quantitative coronary artery stenosis and coronary atherosclerosis imaging: a Consensus Statement from the Quantitative Cardiovascular Imaging Study Group.

The detection and characterization of coronary artery stenosis and atherosclerosis using imaging tools are key for clinical decision-making in patients with known or suspected coronary artery disease. In this regard, imaging-based quantification can be improved by choosing the most appropriate imaging modality for diagnosis, treatment and procedural planning. In this Consensus Statement, we provide clinical consensus recommendations on the optimal use of different imaging techniques in various patient populations and describe the advances in imaging technology. Clinical consensus recommendations on the appropriateness of each imaging technique for direct coronary artery visualization were derived through a three-step, real-time Delphi process that took place before, during and after the Second International Quantitative Cardiovascular Imaging Meeting in September 2022. According to the Delphi survey answers, CT is the method of choice to rule out obstructive stenosis in patients with an intermediate pre-test probability of coronary artery disease and enables quantitative assessment of coronary plaque with respect to dimensions, composition, location and related risk of future cardiovascular events, whereas MRI facilitates the visualization of coronary plaque and can be used in experienced centres as a radiation-free, second-line option for non-invasive coronary angiography. PET has the greatest potential for quantifying inflammation in coronary plaque but SPECT currently has a limited role in clinical coronary artery stenosis and atherosclerosis imaging. Invasive coronary angiography is the reference standard for stenosis assessment but cannot characterize coronary plaques. Finally, intravascular ultrasonography and optical coherence tomography are the most important invasive imaging modalities for the identification of plaques at high risk of rupture. The recommendations made in this Consensus Statement will help clinicians to choose the most appropriate imaging modality on the basis of the specific clinical scenario, individual patient characteristics and the availability of each imaging modality.

Molecular imaging of arterial fibroblast activation protein: association with calcified plaque burden and cardiovascular risk factors.

PURPOSE: We aimed to assess prevalence, distribution, and intensity of in-vivo arterial wall fibroblast activation protein (FAP) uptake, and its association with calcified plaque burden, cardiovascular risk factors (CVRFs), and FAP-avid tumor burden. METHODS: We analyzed 69 oncologic patients who underwent [68 Ga]Ga-FAPI-04 PET/CT. Arterial wall FAP inhibitor (FAPI) uptake in major vessel segments was evaluated. We then investigated the associations of arterial wall uptake with calcified plaque burden (including number of plaques, plaque thickness, and calcification circumference), CVRFs, FAP-positive total tumor burden, and image noise (coefficient of variation, from normal liver parenchyma). RESULTS: High focal arterial FAPI uptake (FAPI +) was recorded in 64/69 (92.8%) scans in 800 sites, of which 377 (47.1%) exhibited concordant vessel wall calcification. The number of FAPI + sites per patient and (FAPI +)-derived target-to-background ratio (TBR) correlated significantly with the number of calcified plaques (FAPI + number: r = 0.45, P < 0.01; TBR: r = - 0.26, P = 0.04), calcified plaque thickness (FAPI + number: r = 0.33, P < 0.01; TBR: r = - 0.29, P = 0.02), and calcification circumference (FAPI + number: r = 0.34, P < 0.01; TBR: r = - 0.26, P = 0.04). In univariate analysis, only body mass index was significantly associated with the number of FAPI + sites (OR 1.06; 95% CI, 1.02 - 1.12, P < 0.01). The numbers of FAPI + sites and FAPI + TBR, however, were not associated with other investigated CVRFs in univariate and multivariate regression analyses. Image noise, however, showed significant correlations with FAPI + TBR (r = 0.30) and the number of FAPI + sites (r = 0.28; P = 0.02, respectively). In addition, there was no significant interaction between FAP-positive tumor burden and arterial wall FAPI uptake (P ≥ 0.13). CONCLUSION: [68 Ga]Ga-FAPI-04 PET identifies arterial wall lesions and is linked to marked calcification and overall calcified plaque burden, but is not consistently associated with cardiovascular risk. Apparent wall uptake may be partially explained by image noise.

PSMA-heterogeneity in metastatic castration-resistant prostate cancer: Circulating tumor cells, metastatic tumor burden, and response to targeted radioligand therapy.

BACKGROUND: We explored the interrelation between prostate-specific membrane antigen (PSMA) expression on circulating tumor cells (CTCs) and that of solid metastatic lesions as determined by whole-body PSMA-targeted positron emission tomography (PET) to refine the prediction of response to subsequent PSMA-targeted radioligand therapy (RLT). METHODS: A prospective study was performed in 20 patients with advanced mCRPC. Of these, 16 underwent subsequent RLT with [177 Lu]Lu-PSMA-617 at a dose of 7.4 GBq every 6-8 weeks. PSMA expression on CTCs using the CellSearch system was compared to clinical and serological results, and to marker expression in targeted imaging and available histological sections of prostatectomy specimens (19% of RLT patients). Clinical outcome was obtained after two cycles of RLT. RESULTS: Marked heterogeneity of PSMA expression was observed already at first diagnosis in available histological specimens. Targeted whole-body imaging also showed heterogeneous inter- and intra-patient PSMA expression between metastases. Heterogeneity of CTC PSMA expression was partially paralleled by heterogeneity of whole-body tumor burden PSMA expression. Twenty percent of CTC samples showed no PSMA expression, despite unequivocal PSMA expression of solid metastases at PET. A high fraction of PSMA-negative CTCs emerged as the sole predictor of poor RLT response (odds ratio [OR]: 0.9379 [95% confidence interval, CI, 0.8558-0.9902]; p = 0.0160), and was prognostic for both shorter progression-free survival (OR: 1.236 [95% CI, 1.035-2.587]; p = 0.0043) and overall survival (OR: 1.056 [95% CI, 1.008-1.141]; p = 0.0182). CONCLUSION: This proof-of-principle study suggests that liquid biopsy for CTC PSMA expression is complementary to PET for individual PSMA phenotyping of mCRPC.

Lack of repeatability of radiomic features derived from PET scans: Results from a 18 F-DCFPyL test-retest cohort.

OBJECTIVES: PET-based radiomic metrics are increasingly utilized as predictive image biomarkers. However, the repeatability of radiomic features on PET has not been assessed in a test-retest setting. The prostate-specific membrane antigen-targeted compound 18 F-DCFPyL is a high-affinity, high-contrast PET agent that we utilized in a test-retest cohort of men with metastatic prostate cancer (PC). METHODS: Data of 21 patients enrolled in a prospective clinical trial with histologically proven PC underwent two 18 F-DCFPyL PET scans within 7 days, using identical acquisition and reconstruction parameters. Sites of disease were segmented and a set of 29 different radiomic parameters were assessed on both scans. We determined repeatability of quantification by using Pearson's correlations, within-subject coefficient of variation (wCOV), and Bland-Altman analysis. RESULTS: In total, 230 lesions (177 bone, 38 lymph nodes, 15 others) were assessed on both scans. For all investigated radiomic features, a broad range of inter-scan correlation was found (r, 0.07-0.95), with acceptable reproducibility for entropy and homogeneity (wCOV, 16.0% and 12.7%, respectively). On Bland-Altman analysis, no systematic increase or decrease between the scans was observed for either parameter (±1.96 SD: 1.07/-1.30, 0.23/-0.18, respectively). The remaining 27 tested radiomic metrics, however, achieved unacceptable high wCOV (≥21.7%). CONCLUSION: Many common radiomic features derived from a test-retest PET study had poor repeatability. Only Entropy and homogeneity achieved good repeatability, supporting the notion that those image biomarkers may be incorporated in future clinical trials. Those radiomic features based on high frequency aspects of images appear to lack the repeatability on PET to justify further study.

Exploring Vessel Wall Biology In Vivo by Ultrasensitive Total-Body PET.

Ultrasensitive, high-resolution, extended-field-of-view total-body (TB) PET using the first-of-its-kind 194-cm axial-field-of-view uEXPLORER may facilitate the interrogation of biologic hallmarks of hitherto difficult-to-evaluate low-signal vessel wall pathology in cardiovascular disease. Methods: Healthy volunteers were imaged serially for up to 12 h after a standard dose of 18F-FDG (n = 15) or for up to 3 h after injection of a very low dose (about 5% of a standard dose; n = 15). A cohort undergoing standard 18F-FDG PET (n = 15) on a conventional scanner with a 22-cm axial field of view served as a comparison group. Arterial wall signal, crosstalk with hematopoietic and lymphoid organs, and image quality were analyzed using standardized techniques. Results: TB PET depicted the large vessel walls with excellent quality. The arterial wall could be imaged with high contrast up to 12 h after tracer injection. Ultralow-dose TB 18F-FDG images yielded a vessel wall signal and target-to-background ratio comparable to those of conventional-dose, short-axial-field-of-view PET. Crosstalk between vessel wall and lymphoid organs was identified with better accuracy in both TB PET cohorts than in conventional PET. Conclusion: TB PET enables detailed assessment of in vivo vessel wall biology and its crosstalk with other organs over an extended time window after tracer injection or at an ultralow tracer dose. These initial observations support the feasibility of serial imaging in low-risk populations and will stimulate future mechanistic studies or therapy monitoring in atherosclerosis and other vessel wall pathologies.

Individual radiosensitivity reflected by γ-H2AX and 53BP1 foci predicts outcome in PSMA-targeted radioligand therapy.

PURPOSE: γ-H2AX and 53BP1 are fundamental for cellular DNA damage response (DDR) after radiation exposure and are linked to cell repair, arrest, or apoptosis. We aimed to evaluate whether DDR-markers in peripheral blood lymphocytes (PBLs) may have predictive potential for outcome in metastatic castration-resistant prostate cancer (mCRPC) patients receiving [177Lu]Lu-prostate-specific membrane antigen (PSMA) radioligand therapy (RLT). METHODS: We prospectively enrolled 20 men with advanced mCRPC scheduled for PSMA-targeted RLT. Prior to the first cycle of [177Lu]Lu-PSMA RLT, all patients underwent [18F]F-PSMA-1007 positron emission tomography (PET)/computed tomography (CT) for assessment of tumor PSMA expression (assessing maximum standardized uptake value (SUVmax) of all tumor lesions). Blood samples were collected prior to, + 1 h after, and + 24 h after administration of [177Lu]Lu-PSMA, and DDR-markers γ-H2AX and 53BP1 were determined in PBLs through immunocytofluorescence. We then tested the predictive performance of DDR-markers relative to clinical and PET-based parameters for progressive disease (PSA-PD) after 2 cycles. In addition, the predictive value for progression-free survival (PSA-PFS, provided as median and 95% confidence interval [CI]) was explored. RESULTS: Low baseline 53BP1 and γ-H2AX foci (P = 0.17) tended to predict early PSA-PD, whereas low SUVmax was significantly associated with higher risk for PSA-PD (P = 0.04). In Kaplan-Meier analysis, there was a trend towards prolonged PSA-PFS in patients with higher baseline 53BP1 of 6 months (mo; 95%CI, 4-9 mo) compared to 3 mo in patients with low 53BP1 (95% CI, 2-3 mo; P = 0.12). Comparable results were recorded for higher γ-H2AX expression (6 mo [95% CI, 3-9 mo] relative to 3 mo [95% CI, 2-4 mo] in patients with low γ-H2AX; P = 0.12). SUVmax, however, did not demonstrate predictive value (P = 0.29). Consistently, in univariate Cox-regression analysis, baseline 53BP1 foci demonstrated borderline significance for predicting PSA-PFS under [177Lu]Lu-PSMA RLT (P = 0.05). CONCLUSION: In this prospective study investigating mCRPC patients undergoing [177Lu]Lu-PSMA RLT, low baseline DDR-markers in PBLs tended to predict poor outcome. Although the study group was small and results need further confirmation, these preliminary findings lay the foundation for exploring additive radiosensitizing or treatment intensification in future studies with high-risk individuals scheduled for RLT.

Parametric Imaging of Biologic Activity of Atherosclerosis Using Dynamic Whole-Body Positron Emission Tomography.

BACKGROUND: For molecular imaging of atherosclerotic vessel wall activity, tracer kinetic analysis may yield improved contrast versus blood, more robust quantitative parameters, and more reliable characterization of systems biology. OBJECTIVES: The authors introduce a novel dynamic whole-body positron emission tomography (PET) protocol that is enabled by rapid continuous camera table motion, followed by reconstruction of parametric data sets using voxel-based Patlak graphical analysis. METHODS: Twenty-five subjects were prospectively enrolled and underwent dynamic PET up to 90 minutes after injection of 2-[18F]fluoro-2-deoxy-D-glucose (FDG). Two sets of images were generated: 1) the established standard of static standardized uptake value (SUV) images; and 2) parametric images of the metabolic rate of FDG (MRFDG) using the Patlak plot-derived influx rate. Arterial wall signal was measured and compared using the volume-of-interest technique, and its association with hematopoietic and lymphoid organ signal and atherosclerotic risk factors was explored. RESULTS: Parametric MRFDG images provided excellent arterial wall visualization, with elimination of blood-pool activity, and enhanced focus detectability and reader confidence. Target-to-background ratio (TBR) from MRFDG images was significantly higher compared with SUV images (2.6 ± 0.8 vs 1.4 ± 0.2; P < 0.0001), confirming improved arterial wall contrast. On MRFDG images, arterial wall signal showed improved correlation with hematopoietic and lymphoid organ activity (spleen P = 0.0009; lymph nodes P = 0.0055; and bone marrow P = 0.0202) and increased with the number of atherosclerotic risk factors (r = 0.49; P = 0.0138), where signal from SUV images (SUVmaxP = 0.9754; TBRmaxP = 0.8760) did not. CONCLUSIONS: Absolute quantification of MRFDG is feasible for arterial wall using dynamic whole-body PET imaging. Parametric images provide superior arterial wall contrast, and they might be better suited to explore the relationship between arterial wall activity, systemic organ networks, and cardiovascular risk. This novel methodology may serve as a platform for future diagnostic and therapeutic clinical studies targeting the biology of arterial wall disease.

The Prognostic Value of Liquid Biopsies for Benefit of Salvage Radiotherapy in Relapsed Oligometastatic Prostate Cancer.

To assess the prognostic value of "liquid biopsies" for the benefit of salvage RT in oligometastatic prostate cancer relapse, we enrolled 44 patients in the study between the years 2016 and 2020. All the patients were diagnosed as having an oligometastatic prostate cancer relapse on prostate-specific membrane antigen (PSMA)-targeted PET-CT and underwent irradiation at the Department of Radiotherapy at the Hannover Medical School. Tumor cells and total RNA, enriched from the liquid biopsies of patients, were processed for the subsequent quantification analysis of relative transcript levels in real-time PCR. In total, 54 gene transcripts known or suggested to be associated with prostate cancer or treatment outcome were prioritized for analysis. We found significant correlations between the relative transcript levels of several investigated genes and the Gleason score, PSA (prostate-specific antigen) value, or UICC stage (tumor node metastasis -TNM classification of malignant tumors from Union for International Cancer Control). Furthermore, a significant association of MTCO2, FOXM1, SREBF1, HOXB7, FDXR, and MTRNR transcript profiles was found with a temporary and/or long-term benefit from RT. Further studies on larger patients cohorts are necessary to prove our preliminary findings for establishing liquid biopsy tests as a predictive examination method prior to salvage RT.

177Lu-PSMA for Extended Treatment of Metastatic Castration-Resistant Prostate Cancer.

To evaluate feasibility, additional benefit and toxicity of treatment extension of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: From 208 patients treated with 177Lu-PSMA every 6-8 weeks, 26 patients who had not progressed and not experienced ≥grade 3 toxicity after 6 cycles continued to receive 177Lu-PSMA until disease progression or complete remission or removal from treatment for toxicity or patient preference. Response rates, the additional benefit of treatment extension, and toxicity were assessed. Results: During treatment extension (up to 13 cycles), 50% of patients achieved an additional PSA decline (-52%±34%, range 1% to 100%), with 8% of patients receiving congruent PSA-based and imaging-based complete response. Median PFS was 450 days. Acute toxicity, including myelosuppression, was mild (≤ grade 2). Xerostomia and chronic kidney disease became more common with repetitive dosing. Conclusion: Extension of 177Lu-PSMA treatment is feasible and effective in mCRPC.

Training on Reporting and Data System (RADS) for Somatostatin-Receptor Targeted Molecular Imaging Can Reduce the Test Anxiety of Inexperienced Readers.

PURPOSE: For somatostatin receptor (SSTR)-positron emission tomography/computed tomography (PET/CT), a standardized framework termed SSTR-reporting and data system (RADS) has been proposed. We aimed to elucidate the impact of a RADS-focused training on reader's anxiety to report on SSTR-PET/CT, the motivational beliefs in learning such a system, whether it increases reader's confidence, and its implementation in clinical routine. PROCEDURES: A 3-day training course focusing on SSTR-RADS was conducted. Self-report questionnaires were handed out prior to the course (Pre) and thereafter (Post). The impact of the training on the following categories was evaluated: (1) test anxiety to report on SSTR-PET/CT, (2) motivational beliefs, (3) increase in reader's confidence, and (4) clinical implementation. To assess the effect size of the course, Cohen's d was calculated (small, d = 0.20; large effect, d = 0.80). RESULTS: Of 22 participants, Pre and Post were returned by 21/22 (95.5%). In total, 14/21 (66.7%) were considered inexperienced (IR, < 1 year experience in reading SSTR-PET/CTs) and 7/21 (33.3%) as experienced readers (ER, > 1 year). Applying SSTR-RADS, a large decrease in anxiety to report on SSTR-PET/CT was noted for IR (d = - 0.74, P = 0.02), but not for ER (d = 0.11, P = 0.78). For the other three categories motivational beliefs, reader's confidence, and clinical implementation, agreement rates were already high prior to the training and persisted throughout the course (P ≥ 0.21). CONCLUSIONS: A framework-focused reader training can reduce anxiety to report on SSTR-PET/CTs, in particular for inexperienced readers. This may allow for a more widespread adoption of this system, e.g., in multicenter trials for better intra- and interindividual comparison of scan results.

High SUVs Have More Robust Repeatability in Patients with Metastatic Prostate Cancer: Results from a Prospective Test-Retest Cohort Imaged with 18F-DCFPyL.

Objectives: In patients with prostate cancer (PC) receiving prostate-specific membrane antigen- (PSMA-) targeted radioligand therapy (RLT), higher baseline standardized uptake values (SUVs) are linked to improved outcome. Thus, readers deciding on RLT must have certainty on the repeatability of PSMA uptake metrics. As such, we aimed to evaluate the test-retest repeatability of lesion uptake in a large cohort of patients imaged with 18F-DCFPyL. Methods: In this prospective, IRB-approved trial (NCT03793543), 21 patients with history of histologically proven PC underwent two 18F-DCFPyL PET/CTs within 7 days (mean 3.7, range 1 to 7 days). Lesions in the bone, lymph nodes (LN), and other organs were manually segmented on both scans, and uptake parameters were assessed (maximum (SUVmax) and mean (SUVmean) SUVs), PSMA-tumor volume (PSMA-TV), and total lesion PSMA (TL-PSMA, defined as PSMA - TV × SUVmean)). Repeatability was determined using Pearson's correlations, within-subject coefficient of variation (wCOV), and Bland-Altman analysis. Results: In total, 230 pairs of lesions (177 bone, 38 LN, and 15 other) were delineated, demonstrating a wide range of SUVmax (1.5-80.5) and SUVmean (1.4-24.8). Including all sites of suspected disease, SUVs had a strong interscan correlation (R 2 ≥ 0.99), with high repeatability for SUVmean and SUVmax (wCOV, 7.3% and 12.1%, respectively). High SUVs showed significantly improved wCOV relative to lower SUVs (P < 0.0001), indicating that high SUVs are more repeatable, relative to the magnitude of the underlying SUV. Repeatability for PSMA-TV and TL-PSMA, however, was low (wCOV ≥ 23.5%). Across all metrics for LN and bone lesions, interscan correlation was again strong (R 2 ≥ 0.98). Moreover, LN-based SUVmean also achieved the best wCOV (3.8%), which was significantly reduced when compared to osseous lesions (7.8%, P < 0.0001). This was also noted for SUVmax (wCOV, LN 8.8% vs. bone 12.0%, P < 0.03). On a compartment-based level, wCOVs for volumetric features were ≥22.8%, demonstrating no significant differences between LN and bone lesions (PSMA-TV, P =0.63; TL-PSMA, P =0.9). Findings on an entire tumor burden level were also corroborated in a hottest lesion analysis investigating the SUVmax of the most intense lesion per patient (R 2, 0.99; wCOV, 11.2%). Conclusion: In this prospective test-retest setting, SUV parameters demonstrated high repeatability, in particular in LNs, while volumetric parameters demonstrated low repeatability. Further, the large number of lesions and wide distribution of SUVs included in this analysis allowed for the demonstration of a dependence of repeatability on SUV, with higher SUVs having more robust repeatability.

Cardiac Fibroblast Activation in Patients Early After Acute Myocardial Infarction: Integration with MR Tissue Characterization and Subsequent Functional Outcome.

After acute myocardial infarction (AMI), fibroblast activation protein (FAP) upregulation exceeds the infarct region. We sought further insights into the physiologic relevance by correlating FAP-targeted PET with tissue characteristics from cardiac MRI (CMR) and functional outcome. Methods: Thirty-five patients underwent CMR, perfusion SPECT, and 68Ga-FAP inhibitor (FAPI)-46 PET/CT within 11 d after AMI. Infarct size was determined from SPECT by comparison to a reference database. For PET, regional SUVs and isocontour volumes of interest determined the extent of cardiac FAP upregulation (FAP volume). CMR yielded functional parameters, area of injury (late gadolinium enhancement [LGE]) and T1/T2 mapping. Follow-up was available from echocardiography or CMR after 139.5 d (interquartile range, 80.5-188.25 d) (n = 14). Results: The area of FAP upregulation was significantly larger than the SPECT perfusion defect size (58% ± 15% vs. 23% ± 17%, P < 0.001) and infarct area by LGE (28% ± 11%, P < 0.001). FAP volume significantly correlated with CMR parameters at baseline (all P < 0.001): infarct area (r = 0.58), left ventricle (LV) mass (r = 0.69), end-systolic volume (r = 0.62), and end-diastolic volume (r = 0.57). Segmental analysis revealed FAP upregulation in 308 of 496 myocardial segments (62%). Significant LGE was found in only 56% of FAP-positive segments, elevated T1 in 74%, and elevated T2 in 68%. Fourteen percent (44/308) of FAP-positive segments exhibited neither prolonged T1 or T2 nor significant LGE. Of note, FAP volume correlated only weakly with simultaneously measured LV ejection fraction at baseline (r = -0.32, P = 0.07), whereas there was a significant inverse correlation with LV ejection fraction obtained at later follow-up (r = -0.58, P = 0.007). Conclusion: Early after AMI and reperfusion therapy, activation of fibroblasts markedly exceeds the hypoperfused infarct region and involves noninfarcted myocardium. The 68Ga-FAPI PET signal does not match regional myocardial tissue characteristics as defined by CMR but is predictive of the evolution of ventricular dysfunction. FAP-targeted imaging may provide a novel biomarker of LV remodeling that is complementary to existing techniques.

[18F]DCFPyL PET/CT for Imaging of Prostate Cancer.

Prostate-specific membrane antigen (PSMA)-directed positron emission tomography (PET) has gained increasing interest for imaging of men affected by prostate cancer (PC). In recent years, 68Ga-labeled PSMA compounds have been widely utilized, although there is a trend towards increased utilization of 18F-labeled agents. Among others, [18F]DCFPyL (piflufolastat F 18, PYLARIFY) has been tested in multiple major trials, such as OSPREY and CONDOR, which provided robust evidence on the clinical utility of this compound for staging, restaging, and change in management. Recent explorative prospective trials have also utilized [18F]DCFPyL PET/CT for response assessment, e.g., in patients under abiraterone or enzalutamide, rendering this 18F-labeled PSMA radiotracer as an attractive biomarker for image-guided strategies in men with PC. After recent approval by the U.S. Food and Drug Administration, one may expect more widespread use, not only in the U.S., but also in Europe in the long term. In the present review, we will provide an overview of the current clinical utility of [18F]DCFPyL in various clinical settings for men with PC.

Pretherapeutic estimated glomerular filtration rate predicts development of chronic kidney disease in patients receiving PSMA-targeted radioligand therapy.

BACKGROUND: Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) may be associated with renal toxicity. We aimed to identify predictive parameters for the development of chronic kidney disease (CKD) in patients with metastatic castration resistant prostate cancer (mCRPC) undergoing RLT. METHODS: In 46 mCRPC patients scheduled for Lu-177-PSMA-RLT, pretherapeutic estimated glomerular filtration rate (eGFR [ml/min/1.73 m2 ]), Tc-99m-mercaptoacetyltriglycine (Tc-99m-MAG3) clearance and baseline Ga-68-PSMA-ligand positron emission tomography (PET)-derived renal cortical uptake and PSMA-tumor volume (TV) were determined. We tested the predictive capability of these parameters and clinical risk factors for the occurrence of CKD (defined as CTCAE vers. 5.0 grade 2 or higher) during follow-up. RESULTS: After 4 ± 3 cycles of RLT average eGFR declined from 76 ± 17 to 72 ± 20 ml/min/1.73 m2 (p = 0.003). Increased estimated renal radiation dose (eRRD) was significantly associated with renal functional decline (p = 0.008). During follow-up, 16/46 (30.4%) developed CKD grade 2 (no grade 3 or higher). In receiver operating characteristic (ROC) analysis, pretherapeutic eGFR was highly accurate in identifying the occurrence of CKD vs no CKD with an area under the curve (AUC) of 0.945 (p < 0.001; best threshold, 77 ml/min/1.73 m2 ), followed by Tc-99m-MAG3-derived tubular extraction rate (TER; AUC, 0.831, p < 0.001; best threshold, 200 ml/min/1.73 m2 ). Renal PET signal (p = 0.751) and PSMA-TV (p = 0.942), however, were not predictive. Kaplan-Meier analyses revealed adverse renal outcome for patients with lower eGFR (p = 0.001) and lower scintigraphy-derived TER (p = 0.009), with pretherapeutic eGFR emerging as the sole predictive parameter in multivariate analysis (p = 0.007). CONCLUSION: Serious adverse renal events are not a frequent phenomenon after PSMA-targeted RLT. However, in patients developing moderate CKD after RLT, pretherapeutic eGFR is an independent predictor for renal impairment during follow-up.