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.

Analysing the tumor transcriptome of prostate cancer to predict efficacy of Lu-PSMA therapy.

RATIONALE: 177Lu-PSMA ([177Lu]Lutetium-PSMA-617) therapy is an effective treatment option for patients with prostate specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer, but still shows a non-responder rate of approximately 30%. Combination regimes of programmed death-ligand 1 (PD-L1) inhibition and concomitant 177Lu-PSMA therapy have been proposed to increase the response rate. However, the interplay of immune landscape and 177Lu-PSMA therapy efficacy is poorly understood. METHODS: Between March 2018 and December 2021, a total of 168 patients were referred to 177Lu-PSMA therapy in our department and received a mean total dose of 21.9 GBq (three cycles in mean). All patients received baseline PSMA positron emission tomography to assess the PSMA uptake. The histopathological specimen of the primary prostate tumor was available with sufficient RNA passing quality control steps for genomic analysis in n=23 patients. In this subset of patients, tumor RNA transcriptomic analyses assessed 74 immune-related features in total, out of which n=24 signatures were not co-correlated and investigated further for outcome prognostication. RESULTS: In the subset of patients who received 177Lu-PSMA therapy, PD-L1 was not significantly associated with OS (HR per SD change (95% CI) 0.74 (0.42 to 1.30); SD: 0.18; p=0.29). In contrast, PD-L2 signature was positively associated with longer OS (HR per SD change 0.46 (95% CI 0.29 to 0.74); SD: 0.24; p=0.001; median OS 17.2 vs 5.7 months in higher vs lower PD-L2 patients). In addition, PD-L2 signature correlated with PSA-response (ϱ=-0.46; p=0.04). The PD-L2 signature association with OS was significantly moderated by L-Lactatdehydrogenase (LDH) levels (Cox model interaction p=0.01). CONCLUSION: Higher PD-L2 signature might be associated with a better response to 177Lu-PSMA therapy and warrants further studies investigating additional immunotherapy. In contrast, PD-L1 was not associated with outcome. The protective effect of PD-L2 signature might be present only in men with lower LDH levels.

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.

Conventional Imaging, MRI and 18F-FDG PET/MRI for N and M Staging in Patients with Newly Diagnosed Breast Cancer.

Background: This study compares the diagnostic potential of conventional staging (computed tomography (CT), axillary sonography and bone scintigraphy), whole-body magnetic resonance imaging (MRI) and whole-body 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/)MRI for N and M staging in newly diagnosed breast cancer. Methods: A total of 208 patients with newly diagnosed breast cancer were prospectively included in this study and underwent contrast-enhanced thoracoabdominal CT, bone scintigraphy and axillary sonography as well as contrast-enhanced whole-body 18F-FDG PET/MRI. The datasets were analyzed with respect to lesion localization and characterization. Histopathology and follow-up imaging served as the reference standard. A McNemar test was used to compare the diagnostic performance of conventional staging, MRI and 18F-FDG PET/MRI and a Wilcoxon test was used to compare differences in true positive findings for nodal staging. Results: Conventional staging determined the N stage with a sensitivity of 80.9%, a specificity of 99.2%, a PPV (positive predictive value) of 98.6% and a NPV (negative predictive value) of 87.4%. The corresponding results for MRI were 79.6%, 100%, 100% and 87.0%, and were 86.5%, 94.1%, 91.7% and 90.3% for 18F-FDG PET/MRI. 18F-FDG PET/MRI was significantly more sensitive in determining malignant lymph nodes than conventional imaging and MRI (p < 0.0001 and p = 0.0005). Furthermore, 18F-FDG PET/MRI accurately estimated the clinical lymph node stage in significantly more cases than conventional imaging and MRI (each p < 0.05). Sensitivity, specificity, PPV and NPV for the M stage in conventional staging were 83.3%, 98.5%, 76.9% and 98.9%, respectively. The corresponding results for both MRI and 18F-FDG PET/MRI were 100.0%, 98.5%, 80.0% and 100.0%. No significant differences between the imaging modalities were seen for the staging of distant metastases. Conclusions:18F-FDG PET/MRI detects lymph node metastases in significantly more patients and estimates clinical lymph node stage more accurately than conventional imaging and MRI. No significant differences were found between imaging modalities with respect to the detection of distant metastases.

Second Version of the Prostate Cancer Molecular Imaging Standardized Evaluation Framework Including Response Evaluation for Clinical Trials (PROMISE V2).

CONTEXT: Prostate-specific membrane antigen (PSMA) targeting positron emission tomography (PET) is emerging to become a reference imaging tool for the staging and restaging of patients with prostate cancer for both clinical routine and trials. The prostate cancer molecular imaging standardized evaluation (PROMISE) criteria have been proposed as a framework for whole-body staging (molecular imaging TNM staging, denoted miTNM staging) to describe the prostate cancer disease extent on PSMA-PET. OBJECTIVE: To create a comprehensive and integrated framework for PSMA-PET image interpretation and reporting. EVIDENCE ACQUISITION: We propose the PROMISE V2 framework, which integrates an updated miTNM system, improved assessment of local disease, and a slightly modified PSMA-expression score for clinical routine. We have added a response monitoring framework defining qualitative and quantitative parameters to be recorded for a longitudinal assessment in clinical trials. EVIDENCE SYNTHESIS: We provide a comprehensive literature review on the current use of the PROMISE framework in clinical research and prospective trials. PROMISE variables demonstrate a clear association with survival. PSMA expression assessed by the PSMA-expression score was used in several trials, and a low PSMA-expression score is a negative prognosticator of overall survival after 177Lu-PSMA radioligand therapy. The proposed imaging parameters recorded for response assessment in clinical trials can be utilized to determine response according to PSMA-PET progression (PPP) or Response Evaluation Criteria in PSMA-PET/Computed Tomography (RECIP) frameworks, but also future response criteria. CONCLUSIONS: PROMISE V2 offers standardized reporting of disease extent for clinical routine and research. Parameters recorded within clinical trials facilitate objective response assessment. PATIENT SUMMARY: Prostate-specific membrane antigen (PSMA) targeting positron emission tomography (PET) has become a standard imaging examination for prostate cancer. We propose a comprehensive framework for the analysis and reporting of PSMA-PET findings that will improve the communication between imaging experts and uro-oncologists.

18F-PSMA Cerenkov Luminescence and Flexible Autoradiography Imaging in a Prostate Cancer Mouse Model and First Results of a Radical Prostatectomy Feasibility Study in Men.

Intraoperative identification of positive resection margins (PRMs) in high-risk prostate cancer (PC) needs improvement. Cerenkov luminescence imaging (CLI) with 68Ga-PSMA-11 is promising, although limited by low residual activity and artificial signals. Here, we aimed to assess the value of CLI and flexible autoradiography (FAR) with 18F-PSMA-1007. Methods: Mice bearing subcutaneous PSMA-avid RM1-PGLS tumors were administered 18F-PSMA-1007, and PET/CT was performed. After the animals had been killed, organs were excised and measured signals in CLI and FAR CLI were correlated with tracer activity concentrations (ACs) obtained from PET/CT. For clinical assessment, 7 high-risk PC patients underwent radical prostatectomy immediately after preoperative 18F-PSMA PET/CT. Contrast-to-noise ratios (CNRs) were calculated for both imaging modalities in intact specimens and after incision above the index lesion. Results: In the heterotopic in vivo mouse model (n = 5), CLI did not detect any lesion. FAR CLI detected a distinct signal in all mice, with a lowest AC of 7.25 kBq/mL (CNR, 5.48). After incision above the index lesion of the prostate specimen, no increased signal was observed at the cancer area in CLI. In contrast, using FAR CLI, a signal was detectable in 6 of 7 patients. The AC in the missed index lesion was 1.85 kBq/mL, resulting in a detection limit of at least 2.06 kBq/mL. Histopathology demonstrated 2 PRMs, neither of which was predicted by CLI or FAR CLI. Conclusion: 18F-PSMA FAR CLI was superior to CLI in tracer-related signal detectability. PC was could be visualized in radical prostatectomy down to 2.06 kBq/mL. However, the detection of PRMs was limited. Direct anatomic correlation of FAR CLI is challenging because of the scintillator overlay.

FDG-PET Positivity and Overall Survival in Renal Cell Carcinoma.

This cohort study examines positron emission tomography in renal cell carcinoma and its association with overall survival among adults.

PSMA PET for the Evaluation of Liver Metastases in Castration-Resistant Prostate Cancer Patients: A Multicenter Retrospective Study.

Background: To evaluate the diagnostic performance of PSMA-PET compared to conventional imaging/liver biopsy in the detection of liver metastases in CRPC patients. Moreover, we evaluated a PSMA-PET/CT-based radiomic model able to identify liver metastases. Methods: Multicenter retrospective study enrolling patients with the following inclusion criteria: (a) proven CRPC patients, (b) PSMA-PET and conventional imaging/liver biopsy performed in a 6 months timeframe, (c) no therapy changes between PSMA-PET and conventional imaging/liver biopsy. PSMA-PET sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for liver metastases were calculated. After the extraction of radiomic features, a prediction model for liver metastases identification was developed. Results: Sixty CRPC patients were enrolled. Within 6 months before or after PSMA-PET, conventional imaging and liver biopsy identified 24/60 (40%) patients with liver metastases. PSMA-PET sensitivity, specificity, PPV, NPV, and accuracy for liver metastases were 0.58, 0.92, 0.82, 0.77, and 0.78, respectively. Either number of liver metastases and the maximum lesion diameter were significantly associated with the presence of a positive PSMA-PET (p < 0.05). On multivariate regression analysis, the radiomic feature-based model combining sphericity, and the moment of inverse difference (Idm), had an AUC of 0.807 (95% CI:0.686-0.920). Conclusion: For liver metastases assessment, [68Ga]Ga-PSMA-11-PET demonstrated moderate sensitivity while high specificity, PPV, and inter-reader agreement compared to conventional imaging/liver biopsy in CRPC patients.

First experiences with dynamic renal [68Ga]Ga-DOTA PET/CT: a comparison to renal scintigraphy and compartmental modelling to non-invasively estimate the glomerular filtration rate.

PURPOSE: The determination of the glomerular filtration rate (GFR) is decisive for a variety of clinical issues, for example, to monitor the renal function in radionuclide therapy patients. Renal scintigraphy using glomerularly filtered tracers allows combined acquisition of renograms and GFR estimation but requires repeated blood sampling for several hours. In contrast, dynamic PET imaging using the glomerularly filtered tracer [68Ga]Ga-DOTA bears the potential to non-invasively estimate the GFR by compartmental kinetic modelling. Here, we report the, to our knowledge, first comparison of human renal dynamic [68Ga]Ga-DOTA PET imaging in comparison to renal scintigraphy and compare PET-derived to serum creatinine-derived GFR measurements. METHODS: Dynamic [68Ga]Ga-DOTA PET data were acquired for 30 min immediately after tracer injection in 12 patients. PET and renal scintigraphy images were visually interpreted in a consensus read by three nuclear medicine physicians. The functional renal cortex was segmented to obtain time-activity curves. The arterial input function was estimated from the PET signal in the abdominal aorta. Single-compartmental tracer kinetic modelling was performed to calculate the GFR using complete 30-min (GFRPET-30) and reduced 15-min PET data sets (GFRPET-15) to evaluate whether a shorter acquisition time is sufficient for an accurate GFR estimation. A modified approach excluding minutes 2 to 10 was applied to reduce urinary spill-over effects. Serum creatinine-derived GFRCKD (CKD-EPI-formula) was used as reference standard. RESULTS: PET image interpretation revealed the same findings as conventional scintigraphy (2/12 patients with both- and 1/12 patients with right-sided urinary obstruction). Model fit functions were substantially improved for the modified approach to exclude spill-over. Depending on the modelling approach, GFRCKD and both GFRPET-30 and GFRPET-15 were well correlated with interclass correlation coefficients (ICCs) from 0.74 to 0.80 and Pearson's correlation coefficients (PCCs) from 0.74 to 0.81. For a subgroup of patients with undisturbed urinary efflux (n = 9), correlations were good to excellent (ICCs from 0.82 to 0.95 and PCCs from 0.83 to 0.95). Overall, GFRPET-30 and GFRPET-15 were excellently correlated (ICCs from 0.96 to 0.99 and PCCs from 0.96 to 0.99). CONCLUSION: Renal [68Ga]Ga-DOTA PET can be a suitable alternative to conventional scintigraphy. Visual assessment of PET images and conventional renograms revealed comparable results. GFR values derived by non-invasive single-compartmental-modelling of PET data show a good correlation to serum creatinine-derived GFR values. In patients with undisturbed urinary efflux, the correlation was excellent. Dynamic PET data acquisition for 15 min is sufficient for visual evaluation and GFR derivation.

Metabolic imaging with FDG-PET and time to progression in patients discontinuing immune-checkpoint inhibition for metastatic melanoma.

BACKGROUND: The optimal duration of immune checkpoint blockade (ICB) therapy is not well established. Active residual disease is considered prohibitive for treatment discontinuation and its detection by diagnostic CT imaging is limited. Here, we set out to determine the potential added value of 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) to identify patients at higher risk of relapse following discontinuation of ICB in advanced melanoma. METHODS: Metastatic melanoma patients who discontinued ICB were identified retrospectively. Eligible patients received FDG-PET and diagnostic CT within four months of ICB discontinuation. We defined morphologic response using RECIST v1.1. Complete metabolic response (CMR) was defined as uptake in tumor lesions below background, whereas any site of residual, FDG-avid disease was rated as non-CMR. The primary endpoint was time to progression (TTP) after therapy discontinuation stratified by morphologic and metabolic imaging response using Kaplan-Meier estimates and log-rank test. RESULTS: Thiry-eight patients were eligible for this analysis. Median follow-up was 37.3 months since ICB discontinuation. Median TTP in the overall cohort was not reached. A greater proportion of patients were rated as CMR in PET (n = 34, 89.5%) as compared to complete response (CR) in CT (n = 13, 34.2%). Median TTP was reached in patients with non-CMR (12.7 months, 95%CI 4.4-not reached) but not for patients with CMR (log-rank: p < 0.001). All patients with complete response by CT had CMR by PET. In a subset of patients excluding those with complete response by CT, TTP remained significantly different between CMR and non-CMR (log-rank: p < 0.001). CONCLUSION: Additional FDG-PET at time of discontinuation of ICB therapy helps identify melanoma patients with a low risk of recurrence and favourable prognosis compared to CT imaging alone. Results may have clinical relevance especially for patients with residual tumor burden.

Comparison of nodal staging between CT, MRI, and [18F]-FDG PET/MRI in patients with newly diagnosed breast cancer.

PURPOSE: To compare CT, MRI, and [18F]-fluorodeoxyglucose positron emission tomography ([18F]-FDG PET/MRI) for nodal status, regarding quantity and location of metastatic locoregional lymph nodes in patients with newly diagnosed breast cancer. MATERIALS AND METHODS: One hundred eighty-two patients (mean age 52.7 ± 11.9 years) were included in this prospective double-center study. Patients underwent dedicated contrast-enhanced chest/abdomen/pelvis computed tomography (CT) and whole-body ([18F]-FDG PET/) magnet resonance imaging (MRI). Thoracal datasets were evaluated separately regarding quantity, lymph node station (axillary levels I-III, supraclavicular, internal mammary chain), and lesion character (benign vs. malign). Histopathology served as reference standard for patient-based analysis. Patient-based and lesion-based analyses were compared by a McNemar test. Sensitivity, specificity, positive and negative predictive values, and accuracy were assessed for all three imaging modalities. RESULTS: On a patient-based analysis, PET/MRI correctly detected significantly more nodal positive patients than MRI (p < 0.0001) and CT (p < 0.0001). No statistically significant difference was seen between CT and MRI. PET/MRI detected 193 lesions in 75 patients (41.2%), while MRI detected 123 lesions in 56 patients (30.8%) and CT detected 104 lesions in 50 patients, respectively. Differences were statistically significant on a lesion-based analysis (PET/MRI vs. MRI, p < 0.0001; PET/MRI vs. CT, p < 0.0001; MRI vs. CT, p = 0.015). Subgroup analysis for different lymph node stations showed that PET/MRI detected significantly more lymph node metastases than MRI and CT in each location (axillary levels I-III, supraclavicular, mammary internal chain). MRI was superior to CT only in axillary level I (p = 0.0291). CONCLUSION: [18F]-FDG PET/MRI outperforms CT or MRI in detecting nodal involvement on a patient-based analysis and on a lesion-based analysis. Furthermore, PET/MRI was superior to CT or MRI in detecting lymph node metastases in all lymph node stations. Of all the tested imaging modalities, PET/MRI showed the highest sensitivity, whereas CT showed the lowest sensitivity, but was most specific.

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.

Lung uptake detected by 68Ga-PSMA-11 PET/CT in prostate cancer patients with SARS-CoV-2: a case series.

Coronavirus disease 2019 (COVID-19) pathology is associated with neoangiogenesis and interstitial pneumonia. 68Ga-PSMA-11-PET/CT is able to image in vivo PSMA (Prostate-Specific Membrane Antigen) expression on both prostate cancer (PCa) cells and neovasculature endothelial cells. The aim of the case series was to explore pulmonary PSMA expression not related to cancer in patients with PCa and concomitant COVID-19. In this retrospective, multicenter case series, patients who underwent 68Ga-PSMA-11-PET/CT for PCa and concomitant proven COVID-19 infection were analyzed. Patients were stratified according to 68Ga-PSMA-11 intensity of uptake in the lung (SUVmax). Low uptake: < blood pool; mild-to-moderate uptake: > blood pool and < liver; intense uptake: > liver. Potential correlation between pulmonary 68Ga-PSMA-11 uptake not related to PCa and CT patterns typical for COVID-19 was assessed. Nine patients were included, all of them presenting abnormal 68Ga-PSMA-11 uptake, at different grades: 2/9 low, 6/9 mild-to-moderate, 1/9 high. Uptake distribution was generally bilateral, peripheral and posterior, positively matching with ground-glass CT alterations in 7/9 (78%) patients, while mismatch was observed in 2/9 (22%). 1/9 patients presented PCa lung metastases at 68Ga-PSMA-11. 68Ga-PSMA-11-PET/CT detected increased PSMA uptake within the lung, not related to PCa, matching with CT typical COVID-19 patterns in almost all patients. Further studies are needed to evaluate the role of 68Ga-PSMA-11 PET in COVID-19 patients and the potential role of PSMA overexpression as a biomarker for neoangiogenesis, in both oncological and infective disorders.

Theranostics in oncology: What radiologists want to know.

Combination of radioligand imaging and therapy, so called radiotheranostics, is a novel tool of precision oncology with proven clinical value. In-depth knowledge of functional imaging nuances is critically needed for precise prognostication and guidance of management. Here, we review theranostic applications with up to Phase III type evidence for outcome improvement: Imaging and therapy of neuroendocrine neoplasms (NEN) exploiting high levels of somatostatin receptor (SSTR) expression and radiotheranostics of prostate cancer targeting the prostate specific membrane antigen (PSMA). This narrative review focusses on these two applications and elucidates patient selection and response assessment by radioligand scintigraphy and/or positron emission tomography. Furthermore, we provide a brief outlook on future applications for novel targets outside of NEN and prostate cancer.

Determining the axillary nodal status with four current imaging modalities including 18F-FDG PET/MRI in newly diagnosed breast cancer: A comparative study using histopathology as reference standard.

Purpose: To compare breast magnetic resonance imaging (MRI), thoracal MRI, thoracal 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET)/MRI and axillary sonography for the detection of axillary lymph node metastases in women with newly diagnosed breast cancer. Materials and Methods: This prospective double-center study included patients with newly diagnosed breast cancer between March 2018 and December 2019. Patients underwent thoracal (18F-FDG PET/)MRI, axillary sonography, and dedicated prone breast MRI. Datasets were evaluated separately regarding nodal status (nodal+ vs. nodal-). Histopathology served as reference standard in all patients. The diagnostic performance of breast MRI, thoracal MRI, thoracal PET/MRI and axillary sonography in detecting nodal positive patients was tested by creating receiver-operating-characteristic curves (ROC) with a calculated area under the curve (AUC). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for all four modalities. A McNemar test was used to assess differences. Results: 112 female patients (mean age 53.04 ± 12.6 years) were evaluated. Thoracal PET/MRI showed the highest ROC-AUC with a value of 0.892. The AUC for breast MRI, thoracal MRI and sonography were 0.782, 0.814 and 0.834, respectively. Differences between thoracal PET/MRI and axillary sonography, thoracal MRI and breast MRI were statistically significant (PET/MRI vs. axillary sonography, P = 0.01; PET/MRI vs. thoracal MRI, P = 0.02; PET/MRI vs. breast MRI, P = 0.03). PET/MRI showed the highest sensitivity (81.8%, 36/44) (95%-CI: 67.29-91.81%) while axillary sonography had the highest specificity (98.5%, 65/66), 95%-CI: 91.84-99.96%). Conclusion: 18F-FDG PET/MRI outperforms axillary sonography, breast MRI and thoracal MRI in determining the axillary lymph node status. In a clinical setting, the combination of 18F-FDG PET/MRI and axillary sonography might be considered to provide even more accuracy in diagnosis.

PSMA-PET for the assessment of metastatic hormone-sensitive prostate cancer volume of disease.

Conventional imaging low-(LVD) versus high-volume disease (HVD) are associated with survival in metastatic hormone-sensitive prostate cancer (mHSPC) according to CHAARTED and STAMPEDE trials. We propose a compatible quantitative PSMA-PET framework for disease volume assessment in mHSPC. Methods: Three PET centers screened their PSMA-PET database for mHSPC patients. CT versus PSMA-PET stage, lesion number, and classification of LVD vs. HVD were determined by one blinded reader; PSMA-positive tumor volume (PSMA-TV) was quantified semi-automatically. Results: 85 CT-based CHAARTED-LVD and 20 CT-based CHAARTED-HVD patients were included. A PSMA-TV of ~40 ml was the optimal cutoff between CT-based CHAARTED-LVD (non-unifocal) and HVD (non-M1c) (AUC 0.86). Stratification into PET-LVD (unifocal or oligometastatic/disseminated <~40 mL) and PET-HVD (oligometastatic/disseminated ≥~40 mL or M1c) had 13% misalignment with CHAARTED criteria. Conclusion: PSMA-PET criteria with volume quantification deliver comparable LVD/HVD discrimination with additional subgroups for unifocal, oligometastatic and disseminated disease, critical for guidance of targeted or multimodal therapy.

Complete metabolic response in patients with advanced nonsmall cell lung cancer with prolonged response to immune checkpoint inhibitor therapy.

INTRODUCTION: Immunotherapy is the new standard of care in advanced nonsmall cell lung cancer (NSCLC). Recently published data show that treatment discontinuation after 12 months of nivolumab treatment is associated with shorter survival. Therefore, the ideal duration of immunotherapy remains unclear, and finding markers of beneficial outcomes is of great importance. Here, we determine the proportion of complete metabolic responses (CMR) in patients who have not progressed after 24 months of immunotherapy. METHODS: This is a retrospective analysis of 45 patients with positron emission tomography using 2-[18F]fluoro-2-deoxy-D-glucose imaging for assessment of residual metabolic activity after at least 24 months. CMR was defined as uptake in tumor lesions below background levels, using mediastinum as a reference. ResultsOut of 45 patients, 29 patients had a CMR (64%). CMR was observed more frequently in non-first-line patients. Patients with CMR were younger (median 65.7 vs 75.5, p=0.03). Fourteen patients with CMR have discontinued therapy and have not progressed until time of analysis; however, median follow-up was only 5.6 (range 0.8-17.0) months. CONCLUSION: After a minimum of 24 months of palliative immunotherapy for NSCLC, CMR occurred in almost two thirds of patients. Potentially, achievement of CMR might identify patients, for whom palliative immunotherapy may be safely discontinued.