Surgery remains the cornerstone of prostate cancer treatment, demanding accurate tumor delineation and margin assessment. The hybrid molecule PSMA-914, which combines positron emission tomography (PET) and near-infrared fluorescence (NIRF) detection capabilities, was developed to improve preoperative imaging and intraoperative guidance during prostate cancer surgery. Methods:In this first-in-human series, prostate cancer patients underwent preoperative PET/CT imaging with 68Ga-labeled PSMA-914 (n = 10), followed by fluorescence-guided surgery after intraoperative PSMA-914 administration (n = 7, doses ranging from 200 -1500 µg/patient). The optimal dose for effective tumor visualization was retrospectively evaluated, and both preoperative and postoperative imaging results were correlated with histopathological findings. Results:Preoperative PET/CT with [68Ga]Ga-PSMA-914 showed high tracer uptake in primary tumors and metastases, facilitating accurate tumor localization. Intraoperatively, PSMA-914 at doses exceeding 1000 µg/patient provided a clear fluorescence signal, allowing for precise tumor and lymph node delineation. This approach significantly aided surgical resection by providing real-time guidance to differentiate malignant tissue from healthy tissue without altering the standard surgical workflow. Histopathological analysis confirmed the accuracy of [68Ga]Ga-PSMA-914 PET/CT staging. The procedure was well tolerated without adverse effects. Conclusion:The dual modality of PSMA-914 has the potential to significantly advance prostate cancer surgery by combining diagnostic imaging and intraoperative guidance. These first results warrant further large-scale clinical trials to validate efficacy and safety across diverse patient populations. The integration of PSMA-914 into clinical protocols promises to benefit prostate cancer surgery by facilitating real-time, high-contrast visualization to aid in complete tumor resection.

Purpose:Diagnosing osteomyelitis in the foot/ankle region is challenging primarily due to anatomical constraints. While bone biopsy is the gold standard, non-invasive methods such as SPECT (single photon emission computed tomography) and MRI are sensitive but lack specificity. This study aims to evaluate SPECT/CT's potential, integrating functional and structural imaging, to improve osteomyelitis diagnosis in this region. Methods:A systematic review following PRISMA guidelines and the Cochrane Handbook was conducted, including comprehensive research across major databases (inception to October 2022). Diagnostic studies using SPECT/CT for suspected foot/ankle bone lesions or inflammation were included. We carried out descriptive analysis, SROC curve generation, and calculated mean sensitivities and specificities. Subgroup analyses were conducted for various tracers, CT resolutions, and evaluation strategies. Sensitivity and heterogeneity analyses, bias risk, and publication bias were assessed. Results:Eleven diagnostic studies (463 patients) were reviewed, with seven focusing on diabetic patients. Tracers included labeled leukocytes (WBC), antigranulocyte antibodies, phosphonates (BS), and gallium citrate. Clinical follow-up was the primary reference standard. Mean sensitivity of SPECT/CT for osteomyelitis diagnosis was 93.8% (95% CI: 89.7-96.4%), and specificity was 84.6% (95% CI: 65.1-94.2%). WBC SPECT/CT was more specific (79.4%) but less sensitive (89.2%) than BS SPECT/CT (specificity 46.5%, sensitivity 93.1%). Combined tracers yielded the highest mean specificity (96.4%). Conclusion:SPECT/CT shows promising diagnostic performance for osteomyelitis in the foot/ankle region, especially when applying combined tracer methods. It is particularly advantageous in chronic, postoperative, and post-traumatic cases, offering added value compared to MRI.

Clinically accurate detection of prostate cancer (PCa) metastases is crucial for management of high-risk PCa patients scheduled for radical prostatectomy. We determine the safety and diagnostic accuracy of pre-operative 68Ga-PSMA-11 PET/CT imaging in newly diagnosed high-risk PCa and assess its impact on patient management. Investigator-initiated prospective multi-center multinational single-arm open-label phase 1/2 imaging trial (EuRadCT 2016–001815-19). Patients with high-risk PCa scheduled for prostatectomy were enrolled at 9 institutions in Germany, Austria, and Switzerland to undergo 68Ga-PSMA-11 PET/CT for primary staging. The primary objectives were the evaluation of 68Ga-PSMA-11 PET/CT imaging to detect the primary tumor and lymph node disease and safety assessment. Secondary objectives included detection of distant metastases, correlation of 68Ga-PSMA-11 uptake with Gleason Score, and determining the impact on clinical management. Impact of pre-operative 68Ga-PSMA-11 PET/CT imaging on target volume definition for radiation therapy was assessed. 173 patients underwent 68Ga-PSMA-11 PET/CT for primary staging. Histopathologic correlation was available in 139 patients (imaging dataset), with lymph node metastases in 55 patients (39.6

The aim of this study was to investigate the accuracy of single-time-point (STP) renal dosimetry imaging using SPECT/CT data, a nonlinear mixed-effects (NLME) model, and a population-based model selection (PBMS) in a large population for 177Lu-labeled prostate-specific membrane antigen therapy. Methods: Biokinetic data (mean ± SD) of [177Lu]Lu-PSMA-617 in kidneys at time points 1 (1.8 ± 0.8 h), 2 (18.7 ± 0.9 h), 3 (42.6 ± 1.0 h), 4 (66.3 ± 0.9 h), and 5 (160.3 ± 24.2 h) after injection were obtained from 63 patients with metastatic castration-resistant prostate cancer using SPECT/CT. Thirteen functions were derived from various parameterizations of 1- to 5-exponential functions. The function's parameters were fitted in the NLME framework to the all-time-point (ATP) data. The PBMS NLME method was performed using the goodness-of-fit test and Akaike weight to select the best function fitting the data. The best function from ATP fitting was used to calculate the reference time-integrated activity and absorbed doses. In STP dosimetry, the parameters of a particular patient with STP data were fitted simultaneously to the STP data at different time points of that patient with ATP data of all other patients. The parameters from STP fitting were used to calculate the STP time-integrated activity and absorbed doses. Relative deviations (RDs) and root-mean-square errors (RMSEs) were used to analyze the accuracy of the calculated STP absorbed dose compared with the reference absorbed dose obtained from the best-fit ATP function. The performance of STP dosimetry using PBMS NLME modeling was compared with the Hänscheid and Madsen methods. Results: The function [Formula: see text] was selected as the best-fit ATP function, with an Akaike weight of 100%. For STP dosimetry, the STP measurement by SPECT/CT at time point 3 (42.6 ± 1.0 h) showed a relatively low mean RD of -4.4% ± 9.4% and median RD of -0.7%. Time point 3 had the lowest RMSE value compared with those at the other 4 time points. The RMSEs of the absorbed dose RDs for time points 1-5 were 23%, 16%, 10%, 20%, and 53%, respectively. The STP dosimetry using the PBMS NLME method outperformed the Hänscheid and Madsen methods for all investigated time points. Conclusion: Our results show that a single measurement of SPECT/CT at 2 d after injection might be used to calculate accurate kidney-absorbed doses using the NLME method and PBMS.

Abstract Background The purpose of this study was to evaluate how a retrospective correction of the partial volume effect (PVE) in [18F]fluoromisonidazole (FMISO) PET imaging, affects the hypoxia discoverability within a gross tumour volume (GTV). This method is based on recovery coefficients (RC) and is tailored for low-contrast tracers such as FMISO. The first stage was the generation of the scanner’s RC curves, using spheres with diameters from 10 to 37 mm, and the same homogeneous activity concentration, positioned in lower activity concentration background. Six sphere-to-background contrast ratios were used, from 10.0:1, down to 2.0:1, in order to investigate the dependence of RC on both the volume and the contrast ratio. The second stage was to validate the recovery-coefficient correction method in a more complex environment of non-spherical lesions of different volumes and inhomogeneous activity concentration. Finally, we applied the correction method to a clinical dataset derived from a prospective imaging trial (DRKS00003830): forty nine head and neck squamous cell carcinoma (HNSCC) cases who had undergone FMISO PET/CT scanning for the quantification of tumour hypoxia before (W0), 2 weeks (W2) and 5 weeks (W5) after the beginning of radiotherapy. Here, PVE was found to cause an underestimation of the activity in small volumes with high FMISO signal. Results The application of the proposed correction method resulted in a statistically significant increase of both the hypoxic subvolume (171% at W0, 691% at W2 and 4.60 × 103% at W5 with p < 0.001) and the FMISO standardised uptake value (SUV) (27% at W0, 21% at W2 and by 25% at W5 with p < 0.001) within the primary GTV. Conclusions The proposed PVE-correction method resulted in a statistically significant increase of the hypoxic fraction (HF) with p < 0.001 and demonstrated results in better agreement with published HF data for HNSCC. To summarise, the proposed RC-based correction method can be a useful tool for a retrospective compensation against PVE.

Chimeric antigen receptor (CAR) T-cell therapy has dramatically shifted the landscape of treatment especially for Non-Hodgkin-Lymphoma (NHL). This study evaluates the role of fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) in NHL treated with CAR T-cell therapy concerning response assessment and prognosis.We evaluated 34 patients with NHL who received a CAR T-cell therapy between August 2019 and July 2022. All patients underwent a pre-therapeutic FDG-PET/CT (PET-0) 6 days prior and a post-therapeutic FDG-PET/CT (PET-1) 34 days after CAR T-cell therapy. Deauville score (DS) was used for evaluation of response to therapy and compared to a minimum follow-up of 5 months.19/34 (55.9%) patients achieved DS ≤ 3 on PET-1, the remaining 15 (44.1%) patients had DS > 3 on PET-1. 14/19 patients with DS ≤ 3 on PET-1 had no relapsed or refractory (r/r)-disease and were still alive at last follow-up. The other 5 patients had r/r-disease and 4 of these died. Except for two patients who had no r/r-disease, all other patients (13/15) with DS > 3 on PET-1 had r/r-disease and 12 of these subsequently died. Patients with DS ≤ 3 on PET-1 had significantly better progression free survival (PFS; HR: 5.7; p < 0.01) and overall survival (OS; HR: 5.0; p < 0.01) compared to patients with DS > 3 on PET-1. In addition, we demonstrated that patients with DS ≤ 4 on PET-0 tended to have longer PFS (HR: 3.6; p = 0.05).Early FDG-PET/CT using the established DS after CAR T-cell therapy is a powerful tool to evaluate response to therapy.

PURPOSE:To develop a CT-based radiomic signature to predict biochemical recurrence (BCR) in prostate cancer patients after sRT guided by positron-emission tomography targeting prostate-specific membrane antigen (PSMA-PET). MATERIAL AND METHODS:Consecutive patients, who underwent 68Ga-PSMA11-PET/CT-guided sRT from three high-volume centers in Germany, were included in this retrospective multicenter study. Patients had PET-positive local recurrences and were treated with intensity-modulated sRT. Radiomic features were extracted from volumes of interests on CT guided by focal PSMA-PET uptakes. After preprocessing, clinical, radiomics, and combined clinical-radiomic models were developed combining different feature reduction techniques and Cox proportional hazard models within a nested cross validation approach. RESULTS:Among 99 patients, median interval until BCR was the radiomic models outperformed clinical models and combined clinical-radiomic models for prediction of BCR with a C-index of 0.71 compared to 0.53 and 0.63 in the test sets, respectively. In contrast to the other models, the radiomic model achieved significantly improved patient stratification in Kaplan-Meier analysis. The radiomic and clinical-radiomic model achieved a significantly better time-dependent net reclassification improvement index (0.392 and 0.762, respectively) compared to the clinical model. Decision curve analysis demonstrated a clinical net benefit for both models. Mean intensity was the most predictive radiomic feature. CONCLUSION:This is the first study to develop a PSMA-PET-guided CT-based radiomic model to predict BCR after sRT. The radiomic models outperformed clinical models and might contribute to guide personalized treatment decisions.

Visual Abstract Quantitative evaluation of prostate-specific membrane antigen (PSMA)–targeting PET/CT remains challenging but is urgently needed for the use of standardized PET-based response criteria, such as the PSMA PET/CT consensus statement or Response Evaluation Criteria in PSMA PET/CT (RECIP 1.0). A recent study evaluated the prognostic value of whole-body tumor volume using a semiautomatic method relying on a 50% threshold of lesion SUVmax (PSMATV50). In the present study, we analyzed the suitability of this approach comparing 18F-PSMA-1007 with 68Ga-PSMA-11 PET/CT scans and the potential of PSMATV50 for the prediction of overall survival (OS) in patients before 177Lu-PSMA radioligand therapy (RLT). Moreover, PSMATV50 was integrated into the PSMA PET/CT consensus statement as well as RECIP 1.0, and the prognostic value of these response classification systems was compared. Methods: This retrospective study included 70 patients with metastatic castration-resistant prostate cancer undergoing PSMA RLT. Thirty-three patients were monitored by 68Ga-PSMA-11 PET/CT, and 37 patients by 18F-PSMA-1007 PET/CT. PET/CT scans before (baseline) and at the end of PSMA RLT after 2–4 cycles (follow-up) were separately analyzed by 2 readers. PSMATV50 at baseline and its change at the time of follow-up (ΔPSMATV50, expressed as a ratio) were correlated with OS using Cox proportional-hazards regression. The results of both subgroups were compared. The integration of ΔPSMATV50 in existing response classification systems was evaluated. To assess and compare the discriminatory strength of these classification systems, Gönen and Heller concordance probability estimates were calculated. Results: PSMATV50 determination was technically feasible in all examinations. A higher PSMATV50 at baseline and a higher ΔPSMATV50 were strongly associated with a shorter OS for both 68Ga-PSMA-11 (PSMATV50: hazard ratio [HR] of 1.29 [95% CI, 1.05–1.55], P = 0.009; ΔPSMATV50: HR of 1.83 [95% CI, 1.08–3.09], P = 0.024) and 18F-PSMA-1007 (PSMATV50: HR of 1.84 [95% CI, 1.13–2.99], P = 0.014; ΔPSMATV50: HR of 1.23 [95% CI, 1.04–1.51], P = 0.03). Response assessment provided high discriminatory power for OS for the PSMA PET/CT consensus statement (concordance probability estimate, 0.73) as well as RECIP 1.0 (concordance probability estimate, 0.74). Conclusion: PSMATV50 and ΔPSMATV50 proved to be predictive of OS not only for 68Ga-PSMA-11 but also for 18F-PSMA-1007 PET/CT scans. Subsequent integration of ΔPSMATV50 into the PSMA PET/CT consensus statement and RECIP 1.0 provided equally high prognostic value for both classification systems.

Background Current studies indicate that fluorine-18-fluorodeoxyglucose positron emission tomography/ computed tomography ([ 18 F]FDG PET/CT) is the most accurate imaging modality for the detection of relapsed locally advanced non-small cell lung cancer (NSCLC) after curatively intended chemoradiotherapy. To this day, there is no objective and reproducible definition for the diagnosis of disease recurrence in PET/CT, the reading of which is relevantly influenced by post radiation inflammatory processes. The aim of this study was to evaluate and compare visual and threshold-based semi-automated evaluation criteria for the assessment of suspected tumor recurrence in a well-defined study population investigated during the randomized clinical PET-Plan trial. Methods This retrospective analysis comprises 114 PET/CT data sets of 82 patients from the PET-Plan multi-center study cohort who underwent [ 18 F]FDG PET/CT imaging at different timepoints for relapse, as suspected by CT. Scans were first analyzed visually by four blinded readers using a binary scoring system for each possible localization and the associated reader certainty of the evaluation. Visual evaluations were conducted repeatedly without and with additional knowledge of the initial staging PET and radiotherapy delineation volumes. In a second step, uptake was measured quantitatively using maximum standardized uptake value (SUVmax), peak standardized uptake value corrected for lean body mass (SULpeak), and a liver threshold-based quantitative assessment model. Resulting sensitivity and specificity for relapse detection were compared to the findings in the visual assessment. The gold standard of recurrence was independently defined by prospective study routine including external reviewers using CT, PET, biopsies and clinical course of the disease. Results Overall interobserver agreement (IOA) of the visual assessment was moderate with a high difference between secure (ĸ = 0.66) and insecure (ĸ = 0.24) evaluations. Additional knowledge of the initial staging PET and radiotherapy delineation volumes improved the sensitivity (0.85 vs 0.92) but did not show significant impact on the specificity (0.86 vs 0.89). PET parameters SUVmax and SULpeak showed lower accuracy compared to the visual assessment, whereas threshold-based reading showed similar sensitivity (0.86) and higher specificity (0.97). Conclusion Visual assessment especially if associated with high reader certainty shows very high interobserver agreement and high accuracy that can be further increased by baseline PET/CT information. The implementation of a patient individual liver threshold value definition, similar to the threshold definition in PERCIST, offers a more standardized method matching the accuracy of experienced readers albeit not providing further improvement of accuracy.

Purpose: With the increased use of focal radiation dose escalation for primary prostate cancer (PCa), accurate delineation of gross tumor volume (GTV) in prostate-specific membrane antigen PET (PSMA-PET) becomes crucial. Manual approaches are time-consuming and observer dependent. The purpose of this study was to create a deep learning model for the accurate delineation of the intraprostatic GTV in PSMA-PET. Methods: A 3D U-Net was trained on 128 different 18F-PSMA-1007 PET images from three different institutions. Testing was done on 52 patients including one independent internal cohort (Freiburg: n = 19) and three independent external cohorts (Dresden: n = 14 18F-PSMA-1007, Boston: Massachusetts General Hospital (MGH): n = 9 18F-DCFPyL-PSMA and Dana-Farber Cancer Institute (DFCI): n = 10 68Ga-PSMA-11). Expert contours were generated in consensus using a validated technique. CNN predictions were compared to expert contours using Dice similarity coefficient (DSC). Co-registered whole-mount histology was used for the internal testing cohort to assess sensitivity/specificity. Results: Median DSCs were Freiburg: 0.82 (IQR: 0.73-0.88), Dresden: 0.71 (IQR: 0.53-0.75), MGH: 0.80 (IQR: 0.64-0.83) and DFCI: 0.80 (IQR: 0.67-0.84), respectively. Median sensitivity for CNN and expert contours were 0.88 (IQR: 0.68-0.97) and 0.85 (IQR: 0.75-0.88) (p = 0.40), respectively. GTV volumes did not differ significantly (p > 0.1 for all comparisons). Median specificity of 0.83 (IQR: 0.57-0.97) and 0.88 (IQR: 0.69-0.98) were observed for CNN and expert contours (p = 0.014), respectively. CNN prediction took 3.81 seconds on average per patient. Conclusion: The CNN was trained and tested on internal and external datasets as well as histopathology reference, achieving a fast GTV segmentation for three PSMA-PET tracers with high diagnostic accuracy comparable to manual experts.

Zusammenfassung Zusammenfassend ergeben sich somit eine Vielzahl an Therapiemöglichkeiten für radiojodrefraktäre differenzierte Schilddrüsenkarzinome (Abb. 1). Primär kann durch eine gezielte Redifferenzierungstherapie eine erneute Radiojodtherapie ermöglicht werden. Des Weiteren stehen mit Sorafenib und Lenvatinib in der Erstlinie der medikamentösen Systemtherapien 2 effektive VEGFR-Inhibitoren zur Verfügung. Lenvatinib wird hierbei als wirksamer angesehen. Bei Versagen von Sorafenib ist der Wechsel auf den noch breiter wirksamen VEGFR/FGFR-Inhibitor Lenvatinib sinnvoll. Bei Progress auf Lenvatinib ist eine molekulare Diagnostik mittels frischer Biopsie notwendig, um spezifische, medikamentös angehbare Läsionen wie BRAF-V600E-, RET- und NTRK-Fusionen zu identifizieren und mittels spezifischer Inhibitoren zu blockieren. Bei Fehlen spezifischer Treibermutationen stehen als Salvage-Therapien Cabozantinib oder die Hinzunahme eines Immuncheckpoint-Inhibitors zur Verfügung.

Background/Purpose: The present study aimed to assess whether SRT to the prostatic fossa should be ini-tiated in a timely manner after detecting biochemical recurrence (BR) in patients with prostate cancer, when no correlate was identified with prostate-specific membrane antigen positron emission tomogra-phy (PSMA-PET). Materials and Methods: This retrospective, multicenter analysis included 1222 patients referred for PSMA-PET after a radical prostatectomy due to BR. Exclusion criteria were: pathological lymph node metastases, prostate-specific antigen (PSA) persistence, distant or lymph node metastases, nodal irradi-ation, and androgen deprivation therapy (ADT). This led to a cohort of 341 patients. Biochemical progression-free survival (BPFS) was the primary study endpoint. Results: The median follow-up was 28.0 months. The 3-year BPFS was 71.6% in PET-negative cases and 80.8% in locally PET-positive cases. This difference was significant in univariate (p = 0.019), but not mul-tivariate analyses (p = 0.366, HR: 1.46, 95%CI: 0.64-3.32). The 3-year BPFS in PET-negative cases was sig-nificantly influenced by age (p = 0.005), initial pT3/4 (p < 0.001), pathology scores (ISUP) >= 3 (p = 0.026), and doses to fossa > 70 Gy (p = 0.027) in univariate analyses. In multivariate analyses, only age (HR: 1.096, 95%CI: 1.023-1.175, p = 0.009) and PSA-doubling time (HR: 0.339, 95%CI: 0.139-0.826, p = 0.017) remained significant. Conclusion: To our best knowledge, this study provided the largest SRT analysis in patients without ADT that were lymph node-negative on PSMA-PET. A multivariate analysis showed no significant difference in BPFS between locally PET-positive and PET-negative cases. These results supported the current EAU rec-ommendation to initiate SRT in a timely manner after detecting BR in PET negative patients. CO 2023 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 184 (2023) 1-8

IntroductionAccurate detection and segmentation of the intraprostatic gross tumor volume (GTV) is pivotal for radiotherapy (RT) in primary prostate cancer (PCa) since it influences focal therapy target volumes and the patients’ cT stage. The study aimed to compare the performance of multiparametric resonance imaging (mpMRI) with [18F] PSMA-1007 positron emission tomography (PET) for intraprostatic GTV detection as well as delineation and to evaluate their respective influence on RT concepts.Materials and MethodsIn total, 93 patients from two German University Hospitals with [18F] PSMA-1007-PET/CT and MRI (Freiburg) or [18F] PSMA-1007-PET/MRI (Dresden) were retrospectively enrolled. Validated contouring techniques were applied for GTV-PET and -MRI segmentation. Absolute tumor volume and cT status were determined for each imaging method. The PCa distribution from histopathological reports based on biopsy cores and surgery specimen was used as reference in terms of laterality (unilateral vs. bilateral).ResultsIn the Freiburg cohort (n = 84), mpMRI and PET detected in median 2 (range: 1–5) and 3 (range: 1–8) GTVs, respectively (p < 0.01). The median GTV-MRI was significantly smaller than the GTV-PET, measuring 2.05 vs. 3.65 ml (p = 0.0005). PET had a statistically significant higher concordance in laterality with surgery specimen compared to mpMRI (p = 0.04) and biopsy (p < 0.01), respectively. PSMA PET led to more cT2c and cT3b stages, whereas cT3a stage was more pronounced in mpMRI. Based on the cT stage derived from mpMRI and PET information, 21 and 23 as well as 59 and 60 patients, respectively, were intermediate- and high-risk according to the National Comprehensive Cancer Network (NCCN) v1.2022 criteria. In the Dresden cohort (n = 9), similar results were observed.ConclusionIntraprostatic GTV segmentation based on [18F] PSMA-1007 PET results in more and larger GTVs compared to mpMRI. This influences focal RT target volumes and cT stage definition, but not the NCCN risk group.

This study aims to evaluate the association of the maximum standardized uptake value (SUVmax) in positron-emission tomography targeting prostate-specific membrane antigen (PSMA-PET) prior to salvage radiotherapy (sRT) on biochemical recurrence free survival (BRFS) in a large multicenter cohort. Patients who underwent 68 Ga-PSMA11-PET prior to sRT were enrolled in four high-volume centers in this retrospective multicenter study. Only patients with PET-positive local recurrence (LR) and/or nodal recurrence (NR) within the pelvis were included. Patients were treated with intensity-modulated-sRT to the prostatic fossa and elective lymphatics in case of nodal disease. Dose escalation was delivered to PET-positive LR and NR. Androgen deprivation therapy was administered at the discretion of the treating physician. LR and NR were manually delineated and SUVmax was extracted for LR and NR. Cox-regression was performed to analyze the impact of clinical parameters and the SUVmax-derived values on BRFS. Two hundred thirty-five patients with a median follow-up (FU) of 24 months were included in the final cohort. Two-year and 4-year BRFS for all patients were 68