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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. [ABSTRACT FROM AUTHOR]

Background: A variety of therapeutic approaches are employed to treat patients suffering from breast cancer. Likewise, a broad spectrum of imaging ligands has been introduced for noninvasive positron emission tomography/computed tomography (PET/CT) imaging to enable comprehensive tumor characterization and more accurate response evaluation. Summary: In recent years, novel radioactively labeled ligands have been developed for PET/CT imaging in metastatic breast cancer. One promising tracer is [18F]fluoroestradiol, which was recently approved by the Food and Drug Administration. It can be used for a whole-body assessment of estrogen receptor status. Another radionuclide currently under development is [68Ga]Ga-fibroblast-activation-protein inhibitor. In addition to new radionuclides, the field of application for existing tracers like [18F]fluorodeoxyglucose (FDG) was broadened. It has been shown that an early therapeutic response to various therapies can be detected by [18F]FDG PET/CT, which leads to early treatment optimization. Key Message: In this review, we highlighted new tracers and applications of PET/CT imaging as well as therapeutic approaches in patients with advanced breast cancer. Furthermore, we give an outlook on the application of artificial intelligence, immunoPET, and liquid biopsy. [ABSTRACT FROM AUTHOR]

Background: The superior accuracy and sensitivity of 18F-FDG-PET/CT in comparison to morphological imaging alone leads to an upstaging in up to 30% of lymphoma patients. Novel digital PET/CT scanners might enable to reduce administered tracer activity or scan time duration while maintaining diagnostic performance; this might allow for a higher patient throughput or a reduced radiation exposure, respectively. In particular, the radiation exposure reduction is of interest due to the often young age and high remission rate of lymphoma patients.Methods: Twenty patients with (suspected) lymphoma (6 for initial staging, 12 after systemic treatment, 2 in suspicion of recurrence) sequentially underwent 18F-FDG-PET/CT examinations on a digital PET/CT (Siemens Biograph Vision) with a total scan time duration of 15 min (reference acquisition protocol) and 5 min (reduced acquisition protocol) using continuous-bed-motion. Both data sets were reconstructed using either standalone time of flight (TOF) or in combination with point spread function (PSF), each with 2 and 4 iterations. Lesion detectability by blinded assessment (separately for supra- and infradiaphragmal nodal lesions and for extranodal lesions), lesion image quantification, and image noise were used as metrics to assess diagnostic performance. Additionally, Deauville Score was compared for all patients after systemic treatment.Results: All defined regions were correctly classified in the images acquired with reduced emission time, and therefore, no changes in staging were observed. Lesion quantification was acceptable, that is, mean absolute percentage deviation of maximum and peak standardized uptake values were 6.8 and 6.4% (derived from 30 lesions). A threefold reduction of scan time duration led to an increase in image noise from 7.1 to 11.0% (images reconstructed with 4 iterations) and from 4.7 to 7.2% (images reconstructed with 2 iterations). No deviations in Deauville Score were observed.Conclusion: These results suggest that scan time duration or administered tracer activity can be reduced threefold without compromising diagnostic performance. Especially a reduction of administered activity might allow for a lower radiation exposure and better health economics. Larger trials are warranted to confirm our results. [ABSTRACT FROM AUTHOR]

To assess the diagnostic accuracy of 68 Ga-labeled fibroblast activation protein inhibitor (FAPI) and 18 F-labeled FDG PET for the detection of various tumors, we performed a head-to-head comparison of both imaging modalities across a range of tumor entities as part of our ongoing 68 Ga-FAPI PET observational trial. Methods: The study included 115 patients with 8 tumor entities who received imaging with 68 Ga-FAPI for tumor staging or restaging between October 2018 and March 2022. Of those, 103 patients received concomitant imaging with 68 Ga-FAPI and 18 F-FDG PET and had adequate lesion validation for accuracy analysis. Each scan was evaluated for the detection of primary tumor, lymph nodes, and visceral and bone metastases. True or false positivity and negativity to detected lesions was assigned on the basis of histopathology from biopsies or surgical excision, as well as imaging validation. Results: 68 Ga-FAPI PET revealed higher accuracy than 18 F-FDG PET in the detection of colorectal cancer ( n = 14; per-patient, 85.7% vs. 78.6%; per-region, 95.6% vs. 91.1%) and prostate cancer ( n = 22; per-patient, 100% vs. 90.9%; per-region, 96.4% vs. 92.7%). 68 Ga-FAPI PET and 18 F-FDG PET had comparable per-patient accuracy in detecting breast cancer ( n = 16, 100% for both) and head and neck cancers ( n = 10, 90% for both modalities). 68 Ga-FAPI PET had lower per-patient accuracy than 18 F-FDG PET in cancers of the bladder ( n = 12, 75% vs. 100%) and kidney ( n = 10, 80% vs. 90%), as well as lymphoma ( n = 9, 88.9% vs. 100%) and myeloma ( n = 10, 80% vs. 90%). Conclusion: 68 Ga-FAPI PET demonstrated higher diagnostic accuracy than 18 F-FDG PET in the diagnosis of colorectal cancer and prostate cancer, as well as comparable diagnostic performance for cancers of the breast and head and neck. Accuracy and impact on management will be further assessed in an ongoing prospective interventional trial (NCT05160051)., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

PET imaging using the somatostatin receptor 2 (SSTR2) antagonist satoreotide trizoxetan (SSO-120, previously OPS-202) could offer accurate tumor detection and screening for SSTR2-antagonist radionuclide therapy in patients with SSTR2-expressing small cell lung cancer (SCLC). The aim of this single-center study was to investigate tumor uptake and detection rates of 68 Ga-SSO-120 in comparison to 18 F-FDG PET in the initial staging of SCLC patients. Methods: Patients with newly diagnosed SCLC who underwent additional whole-body 68 Ga-SSO-120 PET/CT during the initial diagnostic workup were retrospectively included. The mean administered activity was 139 MBq, and the mean uptake time was 60 min. Gold-standard staging 18 F-FDG PET/CT was evaluated if available within 2 wk before or after 68 Ga-SSO-120 PET if morphologic differences in CT images were absent. 68 Ga-SSO-120- or 18 F-FDG-positive lesions were reported in 7 anatomic regions (primary tumor, thoracic lymph node metastases, and distant metastases including pleural, contralateral pulmonary, liver, bone, and other) according to the TNM classification for lung cancer (eighth edition). Consensus TNM staging (derived from CT, endobronchial ultrasound-guided transbronchial needle aspiration, PET, and brain MRI) by a clinical tumor board served as the reference standard. Results: Thirty-one patients were included, 12 with limited and 19 with extensive disease according to the Veterans Administration Lung Study Group classification. 68 Ga-SSO-120-positive tumor was detected in all patients (100%) and in 90 of the 217 evaluated regions (41.5%). Thirteen patients (42.0%) had intense average 68 Ga-SSO-120 uptake (region-based mean SUV max ≥ 10); 28 patients (90.3%) had average 68 Ga-SSO-120 uptake greater than liver uptake (region-based mean peak tumor-to-liver ratio > 1). In 25 patients with evaluable 18 F-FDG PET, primary tumor, thoracic lymph node metastases, and distant metastases were detected in 100%, 92%, and 64%, respectively, of all investigated patients by 68 Ga-SSO-120 and in 100%, 92%, and 56%, respectively, by 18 F-FDG PET. 68 Ga-SSO-120 PET detected additional contralateral lymph node, liver, and brain metastases in 1, 1, and 2 patients, respectively (no histopathology available), and 18 F-FDG PET detected additional contralateral lymph node metastases in 3 patients (1 confirmed, 1 systematic endobronchial ultrasound-guided transbronchial needle aspiration-negative, and 1 without available histopathology). None of these differences altered Veterans Administration Lung Study Group staging. The region-based monotonic correlation between 68 Ga-SSO-120 and 18 F-FDG uptake was low (Spearman ρ = 0.26-0.33). Conclusion: 68 Ga-SSO-120 PET offers high diagnostic precision with comparable detection rates and additional complementary information to the gold standard, 18 F-FDG PET. Consistent uptake in most patients warrants exploration of SSTR2-directed radionuclide therapy., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

We present an overview of our prospective fibroblast-activation protein inhibitor (FAPI) registry study across a 3-y period, with head-to-head comparison of tumor uptake in 68 Ga-FAPI and 18 F-FDG PET, as well as FAP immunohistochemistry. Methods: This is an interim analysis of the ongoing 68 Ga-FAPI PET prospective observational trial at our department. Patients who underwent clinical imaging with 68 Ga-FAPI PET between October 2018 and October 2021 were included. Tracer uptake was quantified by SUV max for tumor lesions and by SUV mean for normal organs. PET tumor volume (40% isocontour) and tumor-to-background ratios were calculated. Correlation between SUV max and FAP staining in tissue samples was analyzed. Results: In total, 324 patients with 21 different tumor entities underwent 68 Ga-FAPI imaging; 237 patients additionally received 18 F-FDG PET. The most common tumor entities were sarcoma (131/324, 40%), pancreatic cancer (67/324, 21%), and primary tumors of the brain (22/324, 7%). The mean primary tumor SUV max was significantly higher for 68 Ga-FAPI than 18 F-FDG among pancreatic cancer (13.2 vs. 6.1, P < 0.001) and sarcoma (14.3 vs. 9.4, P < 0.001), and the same was true for mean SUV max in metastatic lesions of pancreatic cancer (9.4 vs. 5.5, P < 0.001). Mean primary tumor maximum tumor-to-background ratio was significantly higher for 68 Ga-FAPI than 18 F-FDG across several tumor entities, most prominently pancreatic cancer (14.7 vs. 3.0, P < 0.001) and sarcoma (17.3 vs. 4.7, P < 0.001). Compared with 18 F-FDG, 68 Ga-FAPI showed superior detection for locoregional disease in sarcoma (52 vs. 48 total regions detected) and for distant metastatic disease in both sarcoma (137 vs. 131) and pancreatic cancer (65 vs. 57), respectively. Among 61 histopathology samples, there was a positive correlation between 68 Ga-FAPI SUV max and overall FAP immunohistochemistry score ( r = 0.352, P = 0.005). Conclusion: 68 Ga-FAPI demonstrates higher absolute uptake in pancreatic cancer and sarcoma, as well as higher tumor-to-background uptake along with improved tumor detection for pancreatic cancer, sarcoma, and other tumor entities when compared with 18 F-FDG. 68 Ga-FAPI is a new tool for tumor staging with theranostic potential., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Radioembolization is the selective application of radionuclide-loaded microspheres into liver arteries for the therapy of liver tumours and metastases. In this review, we focused on therapy planning and dosimetry, as well as the main indications of 90Y-glass and resin microspheres and 166Ho-microspheres., Competing Interests: The Department of Radiology and Nuclear Medicine of the UMC Utrecht receives royalties and research support from Quirem Medical and Terumo. ML is a consultant for BTG, Terumo and Quirem Medical.HA, LS, HI report receiving lectureship compensations fees by SIRTeX Medical Euro.MS declares that she has no conflict of interest, (Thieme. All rights reserved.)

Fibroblast activation protein inhibitor (FAPI) PET/CT is a new tool in the diagnostic workup of cancer. With a growing volume of applications, pitfalls and common findings need to be considered for 68 Ga-FAPI PET/CT image interpretation. The aim of this study was to summarize common findings and report pitfalls in 68 Ga-FAPI PET/CT. Methods: Ninety-one patients underwent whole-body PET/CT with either FAPI-04 ( n = 25) or FAPI-46 ( n = 66). Findings were rated in a consensus session of 2 experienced readers. Pitfalls and common findings were defined as focal or localized uptake above the background level and categorized as unspecific or nonmalignant and grouped into degenerative, muscular, scarring/wound-healing, uterine, mammary gland, and head-and-neck findings. The frequency of findings was reported on a per-patient and per-group basis, and SUV max , SUV mean , and SUV peak were measured. Results: Non-tumor-specific uptake was found in 81.3% of patients. The most frequent finding was uptake in degenerative lesions (51.6%), with a mean SUV max of 7.7 ± 2.9, and head-and-neck findings (45.1%). Except for the salivary glands, the uptake values did not differ between 10 and 60 min after injection in most findings. Uterine uptake was found in most women (66.7%), with a mean SUV max of 12.2 ± 7.3, and uptake correlated negatively with age (SUV max , r = -0.6, P < 0.01; SUV peak , r = -0.57, P < 0.01; SUV mean , r = -0.58, P < 0.01). Conclusion: Pitfalls include non-tumor-specific 68 Ga-FAPI uptake in degenerative lesions, muscle, the head and neck, scarring, the mammary glands, or the uterus. Here, we summarize the findings to help readers avoid common mistakes at centers introducing 68 Ga-FAPI PET/CT., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and the third most frequent cause of cancer-related death. A growing number of local and systemic therapies are available, and accurate staging is critical for management decisions. We assessed the impact of neovasculature imaging by 68 Ga-PSMA-11 PET/CT on disease staging, prognostic groups, and management of patients with HCC compared with staging with CT. Methods: Forty patients who received imaging with 68 Ga-PSMA-11 PET/CT for HCC staging between September 2018 and September 2019 were retrospectively included. Management before and after PET scanning was assessed by standardized surveys. The presence of HCC was evaluated by 3 masked readers on a per-patient and per-region basis for PET/CT (PET criteria) and multiphase contrast-enhanced CT (CT criteria) in separate sessions. Lesions were validated by follow-up imaging or histopathology, and progression-free survival was recorded. Endpoints were detection rate and positive predictive value for 68 Ga-PSMA-11 PET versus CT, interreader reproducibility, and changes in stage, prognostic groups, and management plans. Results: Median age was 65 y (range, 37-81 y), and median Child-Pugh score was 5 (range, 5-9). Most patients were treatment-naïve (27/40, 67.5%). The sensitivity of PET versus CT to identify liver lesions for patients with lesion validation was 31 of 32 (97%) for both modalities, whereas it was 6 of 6 (100%) versus 4 of 6 (67%), respectively, for extrahepatic lesions. PET and CT each had a positive predictive value of 100% at the liver level. PET versus CT stage was congruent in 30 of 40 (75%) patients; upstaging was seen in 8 of 40 patients (20%), whereas 2 of 40 (5%) had downstaging by PET. Intended management changed in 19 of 40 patients (47.5%); 9 of 19 of these patients were found to have detectable distant metastases (47.4%) and assigned stage 4 disease, most of whom were shifted to systemic therapy (8/9, 89%). Two patients underwent 177 Lu-PSMA-617 radioligand therapy. Median progression-free survival was 5.2 mo for the entire cohort; 5.3 mo for PET M0, and 4.7 mo for PET M1 patients, respectively. Conclusion: 68 Ga-PSMA-11 PET demonstrated higher accuracy than CT in the detection of HCC metastases and was associated with a management change in about half the patient cohort., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)