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Purpose: We wanted to establish the range of Ga-DOTA-TOC uptake in liver and bone metastases of patients with neuroendocrine tumours (NET) and to establish the range of its uptake in pancreatic NET. This would allow differentiation between physiological uptake and tumour-related somatostatin receptor expression in the pancreas (including the uncinate process), liver and bone. Finally, we wanted to test for differences in patients with NET, either treated or not treated with peptide receptor radionuclide therapy (PRRT). Methods: In 249 patients, 390 Ga-DOTA-TOC PET/CT studies were performed. The clinical indications for PET/CT were gastroenteropancreatic NET (194 studies), nongastroenteropancreatic NET (origin in the lung and rectum; 46 studies), NET of unknown primary (111 studies), phaeochromocytoma/glomus tumours (18 studies), and radioiodine-negative metastatic thyroid carcinoma (21 studies). Results: SUV (mean ± standard deviation) values of Ga-DOTA-TOC were 29.8 ± 16.5 in 162 liver metastases, 19.8 ± 18.8 in 89 bone metastases and 34.6 ± 17.1 in 43 pancreatic NET (33.6 ± 14.3 in 30 tumours of the uncinate process and 36.3 ± 21.5 in 13 tumours of the pancreatic tail). A significant difference in SUV ( p < 0.02) was found in liver metastases of NET patients treated with PRRT. There were significant differences in SUV between nonmalignant and malignant tissue for both bone and liver metastases and for pancreatic NET including the uncinate process ( p < 0.0001). At a cut-off value of 17.1 the specificity and sensitivity of SUV for differentiating tumours in the uncinate process were 93.6 % and 90.0 %, respectively ( p < 0.0001). Conclusion: Ga-DOTA-TOC is an excellent tracer for the imaging of tumours expressing somatostatin receptors on the tumour cell surface, facilitating the detection of even small tumour lesions. The noninvasive PET/CT approach by measurement of regional SUV can offer important clinical information to distinguish between physiological and pathological somatostatin receptor expression, especially in the uncinate process. PRRT does not significantly influence SUV, except in liver metastases of patients with NET. [ABSTRACT FROM AUTHOR]

Several exploratory studies have demonstrated the feasibility of cholecystokinin-2 receptor (CCK2R) targeting in patients with medullary thyroid carcinoma (MTC) and other neuroendocrine tumors (NETs). We report the results of a prospective phase I/IIA pilot study (clinicaltrials.gov NCT06155994) conducted at our center with the 68 Ga-labeled peptide analog DOTA-DGlu-Ala-Tyr-Gly-Trp-(N-Me)Nle-Asp-1-Nal-Phe-NH 2 ( 68 Ga-DOTA-MGS5). Methods: Six patients with advanced MTC and 6 patients with gastroenteropancreatic and bronchopulmonary NETs confirmed by previous PET/CT imaging with other PET tracers received a single dose of 180 MBq of 68 Ga-DOTA-MGS5. The first 6 patients enrolled in the study were included in the dosimetry evaluation, and safety was assessed in all 12 patients. PET/CT imaging was performed at different time points after injection to perform dosimetric calculations and to determine the optimal imaging time window. In addition, blood and urine samples were collected for pharmacokinetic assessments. Results: The administration of 68 Ga-DOTA-MGS5 was well tolerated, with minor adverse drug reactions occurring only in 3 patients. 68 Ga-DOTA-MGS5 was cleared rapidly from the blood, with less than 21% of the injected activity present in blood 215 ± 10 min after injection. Tracer elimination occurred mainly through the kidneys, with a cumulative urinary excretion greater than 40% 3 h after injection. A high percentage of intact radiopeptide was confirmed in plasma. The highest absorbed dose was found for the urinary bladder wall, the stomach wall, and the kidneys, with an effective dose of 0.023 ± 0.007 mSv/MBq. The time points of 1 and 2 h after injection proved to be optimal for PET/CT imaging. In the 6 patients included in the dosimetry evaluation, local metastasis was confirmed in 2 patients with advanced MTC, whereas only 1 of 4 patients with gastroenteropancreatic NETs was positive in 68 Ga-DOTA-MGS5 PET/CT. Conclusion: Besides confirming the safety of administration, within the phase I part of the prospective clinical trial, an acceptable effective whole-body dose, an overall favorable biodistribution, and the feasibility of cholecystokinin-2 receptor imaging could be shown for 68 Ga-DOTA-MGS5., (© 2025 by the Society of Nuclear Medicine and Molecular Imaging.)

Objective: This retrospective study aimed to analyse the correlation between somatostatin receptor subtypes (SSTR 1-5) and maximum standardized uptake value (SUV max ) in meningioma patients using Gallium-68 DOTA-D-Phe1-Tyr3-octreotide Positron Emission Tomography ([68Ga]Ga-DOTATOC PET). Secondly, we developed a radiomic model based on apparent diffusion coefficient (ADC) maps derived from diffusion weighted magnetic resonance images (DWI MRI) to reproduce SUV max ., Method: The study included 51 patients who underwent MRI and [68Ga]Ga-DOTATOC PET before meningioma surgery. SUV max values were quantified from PET images and tumour areas were segmented on post-contrast T1-weighted MRI and mapped to ADC maps. A total of 1940 radiomic features were extracted from the tumour area on each ADC map. A random forest regression model was trained to predict SUV max and the model's performance was evaluated using repeated nested cross-validation. The expression of SSTR subtypes was quantified in 18 surgical specimens and compared to SUV max values., Results: The random forest regression model successfully predicted SUV max values with a significant correlation observed in all 100 repeats (p < 0.05). The mean Pearson's r was 0.42 ± 0.07 SD, and the root mean square error (RMSE) was 28.46 ± 0.16. SSTR subtypes 2A, 2B, and 5 showed significant correlations with SUV max values (p < 0.001, R2 = 0.669; p = 0.001, R2 = 0.393; and p = 0.012, R2 = 0.235, respectively)., Conclusion: SSTR subtypes 2A, 2B, and 5 correlated significantly with SUV max in meningioma patients. The developed radiomic model based on ADC maps effectively reproduces SUV max using [68Ga]Ga-DOTATOC PET., (© 2023. The Author(s).)

PET/CT with the new 68 Ga-labeled minigastrin analog DOTA-dGlu-Ala-Tyr-Gly-Trp-( N -Me)Nle-Asp-1-Nal-NH 2 ( 68 Ga-DOTA-MGS5) was performed on patients with advanced medullary thyroid cancer (MTC) to evaluate cholecystokinin-2 receptor expression status. Methods: Six patients with advanced MTC underwent PET/CT with 68 Ga-DOTA-MGS5. From the images acquired 1 and 2 h after injection, preliminary data on the biodistribution and tumor-targeting properties were evaluated in a retrospective analysis. Results: In total, 87 lesions with increased radiotracer uptake considered malignant were detected (2 local recurrences, 8 lymph node lesions, 27 liver lesions, and 50 bone lesions). In general, radiotracer accumulation in lesions was higher at 2 h than at 1 h after injection (mean SUV max , 7.2 vs. 6.0, respectively; mean SUV mean , 4.4 vs. 3.6, respectively). Conclusion: The preliminary results clearly demonstrate the potential of 68 Ga-DOTA-MGS5 PET/CT in detecting local recurrence and metastases in patients with advanced MTC., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Radiation necrosis represents a potentially devastating complication after radiation therapy in brain tumors. The establishment of the diagnosis and especially the differentiation from progression and pseudoprogression with its therapeutic implications requires interdisciplinary consent and monitoring. Herein, we want to provide an overview of the diagnostic modalities, therapeutic possibilities and an outlook on future developments to tackle this challenging topic. The aim of this report is to provide an overview of the current morphological, functional, metabolic and evolving imaging tools described in the literature in order to (I) identify the best criteria to distinguish radionecrosis from tumor recurrence after the radio-oncological treatment of malignant gliomas and cerebral metastases, (II) analyze the therapeutic possibilities and (III) give an outlook on future developments to tackle this challenging topic. Additionally, we provide the experience of a tertiary tumor center with this important issue in neuro-oncology and provide an institutional pathway dealing with this problem.

Patients and Methods: Six post COVID-19 patients suspected for pulmonary fibrosis were scheduled for dual-tracer PET/CT with 18 F-FDG and 68 Ga-fibroblast activation protein inhibitor (FAPI)-46. The uptake of 68 Ga-FAPI-46 in the involved lung was compared with a control group of 9 non-COVID-19 patients. Clinical data and PET/CT imaging were collected and analyzed., Results: PET/CT revealed in all 6 pulmonary impaired patients the reduced glucose avidity on 18 F-FDG and clear positivity on 68 Ga-FAPI-46 PET/CT in comparison to the control group., Conclusions: Enhancing fibrotic repair mechanisms, 68 Ga-FAPI PET/CT may improve noninvasive clinical diagnostic performance in patients with long-term CT abnormalities after severe COVID-19. Although this study shows promising results, additional studies in larger populations are required to establish a general diagnostic guideline., Competing Interests: Conflicts of interest and sources of funding: F.L.G. is an advisor at ABX, SOFIE Biosciences, and Telix Pharmaceutical. F.L.G. and U.H. have a patent application for quinolone-based FAP-targeting agents for imaging and therapy in nuclear medicine and also have shares of a consultancy group for iTheranostics. No conflicts of interest exist for A.B., A.S., S.S., G.S., J.F., C.U., B.N., I.T., G.W., I.V., and J.L.R., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Overlap syndromes of anti-NMDA receptor encephalitis and MOG-mediated demyelination have been reported. In this case we provide a long-term longitudinal follow-up of clinical and imaging characteristics as well as of antibody dynamics., Case Presentation: We report a 32-year-old male patient who presented with psychosis, decreased consciousness and movement disorders and was tested positive for anti-NMDA receptor antibodies. Forty-four months after symptom onset and diagnosis of autoimmune encephalitis, he suffered from relapse. At this time, the patient developed anti-MOG and anti-Caspr2 antibodies. Treatment with plasmapheresis, steroids and rituximab eventually led to substantial clinical and radiological improvement. Anti-Caspr2 antibodies persisted, anti-NMDA receptor antibodies decreased, while anti-MOG antibodies turned negative again., Conclusion: We provide long-term longitudinal follow-up of a patient with anti-NMDA receptor encephalitis who developed triple antibody positivity at the time of relapse. Antibody dynamics were associated with clinical disease course., (© 2022. The Author(s).)

Background: Gastrin-releasing peptide receptors (GRPRs) are molecular imaging targets in multiple malignancies. Recently, NeoBOMB1, a 68Ga-labelled antagonist to GRPRs, was developed for PET. Here we report the outcome of a Phase I/IIa clinical trial (EudraCT 2016-002053-38) describing diagnostic properties and covariates influencing uptake of 68Ga-NeoBOMB1 in oligometastatic gastrointestinal stromal tumor (GIST) patients. Methods: Nine patients with advanced GIST using PET/CT (computed tomography) were included. After kit-based 68Ga-NeoBOMB1 preparation with a licensed 68Ge/68Ga generator, 3 MBq/kg body weight were injected intravenously. PET/CT included dynamic and static PET scans 5, 12 and 18 min and 1, 2, and 3−4 h post injection (first six patients) and static PET scans 2 and 3−4 h post injection (last three participants). Tumor targeting was assessed on a per-lesion and per-patient basis. Results: Six patients showed visible radiotracer uptake in at least one tumor lesion. Seventeen out of 37 tumor lesions exhibited significant 68Ga-NeoBOMB1 uptake (median SUVmax 11.8 [range 2.8−51.1] 2 h p.i. and 13.2 [range 2.5−53.8] 3−4 h p.i) and improved lesion-to-background contrast over time. Five lesions (13.5%) were identified only by 68Ga-NeoBOMB1-PET, with no correlation on contrast-enhanced CT. Three patients showed no radiotracer accumulation in any lesions. Tracer uptake correlated with male sex (p < 0.0001), higher body mass index (p = 0.007), and non-necrotic lesion appearance (p = 0.018). There was no association with whole-lesion contrast enhancement, hepatic localization, mutational status, or disease duration. Conclusions: 68Ga-NeoBOMB1-PET exhibits variable tumor uptake in advanced-stage GIST patients, correlating with lesion vitality based on CT contrast uptake, opening the possibility of a theragnostic approach in selected cases.

An individual patient meta-analysis followed 1216 patients with PSA-only recurrence (biochemical recurrence, BCR) restaged with [68Ga]Ga-PSMA-11 PET/CT before the salvage treatment for median 3.5 years and analyzed the overall survival (OS). A new risk model included a good risk group with a prescan PSA < 0.5 ng/mL (26%), an intermediate risk group with a prescan PSA > 0.5 ng/mL and a PSMA PET/CT with 1 to 5 positive sites (65%), and a poor risk group with a prescan PSA > 0.5 ng/mL and a PSA PET/CT with > 5 positive sites (9%) (p < 0.0001, log rank test). The poor risk group had a five-year OS > 60%. Adding a BCR risk score by the European Association of Urology did not significantly improve the prediction of OS (p = 0.64). In conclusion, the restaging PSMA PET/CT markedly predicted the 5-year OS. The new risk model for patients with PSA-only relapse requires a restaging PSMA PET/CT for patients with a prescan PSA > 0.5 ng/mL and has a potential use in new trials aiming to improve the outcome for patients with PSA-only recurrence who have polysites prostate cancer detected on PSMA PET/CT.

Purpose: The aims of this study were to evaluate the diagnostic accuracy of the dual imaging method combining cardiac iodine- 123 -metaiodobenzylguanidine single-photon emission computed tomography combined with low-dose chest computed tomography compared to routine cardiac scintigraphy, and assess regional differences in tracer distribution and the relationships between imaging and autonomic function in Parkinson's disease and multiple system atrophy., Methods: A prospective study including 19 Parkinson's disease and 12 multiple system atrophy patients was performed. Patients underwent clinical evaluation, iodine- 123 -metaiodobenzylguanidine single-photon emission computed tomography combined with chest computed tomography, planar scintigraphy, and cardiovascular autonomic function tests., Results: Co-registration of single-photon emission computed tomography and chest computed tomography resulted in three groups with distinct patterns of tracer uptake: homogeneous, non-homogeneously reduced and absent. There was a significant difference in group allocation among patients with multiple system atrophy and Parkinson's disease (p = 0.001). Most multiple system atrophy patients showed homogeneous uptake, and the majority of Parkinson's disease patients showed absent cardiac tracer uptake. We identified a pattern of heterogeneous cardiac tracer uptake in both diseases with reductions in the apex and the lateral myocardial wall. Sympathetic dysfunction reflected by a missing blood pressure overshoot during Valsalva manoeuvre correlated with cardiac tracer distribution in Parkinson's disease patients (p < 0.001)., Conclusions: The diagnostic accuracy of the dual imaging method and routine cardiac scintigraphy were similar. Anatomical tracer allocation provided by the dual imaging method of cardiac iodine- 123 -metaiodobenzylguanidine single-photon emission computed tomography and chest computed tomography identified a heterogeneous subgroup of Parkinson's disease and multiple system atrophy patients with reduced cardiac tracer uptake in the apex and the lateral wall. Sympathetic dysfunction correlated with cardiac imaging in Parkinson's disease patients., (© 2022. The Author(s).)

The aim of this study was twofold. First, we aimed to assess the impact of forced diuresis with early furosemide injection on the detection rate of local recurrence in prostate cancer patients with biochemical recurrence referred for 68 Ga-labeled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC ( 68 Ga-PSMA-11) PET/CT. Second, we determined whether intravenous administration of furosemide shortly after tracer injection increases renal washout of 68 Ga-PSMA-11 before it binds to the PSMA receptor with possible influence on biodistribution and intensity of tracer uptake in organs with physiologic tracer accumulation. Methods: In a retrospective analysis, 2 different groups with 220 prostate cancer patients each, referred for 68 Ga-PSMA-11 PET/CT because of biochemical recurrence after primary therapy, were compared: patients in group 1 (median prostate-specific antigen, 1.30 ng/mL) received no preparation before imaging, whereas patients in group 2 (median prostate-specific antigen, 0.82 ng/mL) were injected with 20 mg of furosemide and 500 mL of sodium chloride (NaCl 0.9%) immediately after tracer injection. The presence of local recurrence was assessed visually. In addition, the intensity of tracer accumulation in organs with physiologic tracer uptake was evaluated. Results: The detection rate of lesions judged positive for local recurrence was significantly higher in patients receiving furosemide than in patients without preparation: 56 cases (25.5%) versus 38 cases (17.3%), respectively ( P = 0.048). Median maximum SUVs (SUV max ) of organs with physiologic uptake of 68 Ga-PSMA-11 in groups 1 and 2 were urinary bladder (63.0 vs. 8.9), kidney (55.6 vs. 54.5), liver (9.9 vs. 9.4), spleen (11.2 vs. 11.9), small bowel (16.2 vs. 17.1), parotid gland (19.2 vs. 19.6), lacrimal gland (8.9 vs. 10.9), blood-pool activity (2.2 vs. 2.3), muscle (1.0 vs. 1.1), and bone (1.6 vs. 1.6). Apart from bladder activity, no significant reduction of tracer accumulation was found in the patient group receiving furosemide. Conclusion: Injection of 20 mg of furosemide at the time point of radiotracer administration significantly increases the detection rate of local recurrence in prostate cancer patients with biochemical recurrence referred for 68 Ga-PSMA-11 PET/CT. As intensity of 68 Ga-PSMA-11 uptake in organs with physiologic uptake is not significantly reduced, a negative impact of early furosemide injection on targeting properties and biodistribution of 68 Ga-PSMA-11 seems unlikely., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Primary pericardial mesothelioma (PPM) is a rare form of highly aggressive cancer. Many patients are diagnosed only at an advanced stage. Therefore, the overall survival rate is poor with a median survival of 3 months. In some rare cases, the PPM infiltrates the myocardium causing lethal myocardial dysfunction., Case Summary: A 66-year-old patient was transferred to our centre with the provisional diagnose of pericarditis of unknown origin. Using extensive cardiac imaging [echocardiography, computed tomography (CT), positron emission tomography-CT, cardiac magnetic resonance imaging, left and right heart catheterization, coronary angiography], PPM was finally diagnosed. After consultation with the oncologists, the heart team decided to resect the tumour first due to impaired haemodynamics and then initiate adjuvant chemotherapy. Intraoperatively, myocardial infiltration of the tumour became apparent, which was not detected preoperatively despite intensive imaging. Complete resection of the PPM was not possible and effective decompression of the ventricle could not be achieved. The patient died on the first postoperative day., Discussion: Surgical therapy is indicated in many forms of cardiac tumours. However, when a tumour invades the myocardium, surgery often comes to its limits. In this case, myocardial invasion of PPM could not be detected despite extensive imaging. We therefore suggest that possible myocardial infiltration by PPM, and thus potential limitations of cardiac surgery, should be considered independently of imaging results when therapeutic options are discussed., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: 68Ga-PSMA-11 PET/CT is a promising method for the assessment of local recurrence (LR) in prostate cancer (PCa) patients. The aim of this study was to evaluate the diagnostic performance of early 68Ga-PSMA-11 PET imaging in comparison to 68Ga-PSMA-11 PET imaging 60 min post-injection (p.i.) in the detection of LR in patients with biochemical recurrence (BR) of prostate carcinoma., Materials and Methods: 190 image sets of patients with BR in PCa who underwent 68Ga-PSMA-11 PET/CT were assessed retrospectively (median prostate specific antigen (PSA) value, 0.70 ng/mL (range, 0.1-105.6 ng/mL)). Patients received an early static scan of the pelvic area (median, 248 s p.i. (range, 56-923 s)) and a whole-body scan 60 min p.i. (median, 64 min p.i. (range, 45-100 min)) with intravenous administration of 20 mg furosemide i.v. at the time of tracer application, followed by intravenous hydration with 500 mL of sodium chloride (NaCl 0.9%). Assessment was based on visual analysis and calculation of the maximum standardized uptake value (SUVmax) of the pathologic lesions present in the prostate fossa found in the early PET imaging and 60 min PET scans. The scans were characterized as negative, positive, or equivocal. The results were compared, and the combination of early and 60 min p.i. imaging was evaluated., Results: Image assessment resulted in 30 (15.8%) positive, 17 (8.9%) equivocal, and 143 (75.3%) negative findings in early scans, and 28 (14.7%) positive, 25 (13.2%) equivocal, and 137 (72.1%) negative findings of LR in 60 min p.i. images. For combined image analysis, 33 (17.4%) cases were positive and 20 (10.5%) were equivocal. There was no statistical significance between the number of positive ( p = 0.815), negative ( p = 0.327), and equivocal ( p = 0.152) findings. Furthermore, the combination of both scans showed no statistically significant differences for the positive and negative findings ( p = 0.063). The median SUVmax was 4.9 (range, 2.0-55.2) for positive lesions in the early scans and 8.0 (range, 2.1-139.9) in the scans 60 min p.i. The median SUVmax for bladder activity was 2.5 (range, 0.9-12.2) in the early scans and 8.2 (range, 1.8-27.6) in the scans 60 min p.i., Conclusion: Early static imaging additional to 68Ga-PSMA-11 PET images acquired 60 min p.i. has limited value in patients prepared with furosemide and hydration, and showed no statistically significant change in the detection rate (DR) of LR and the number of equivocal findings. Based on our results, in departments following a protocol with forced diuresis, including furosemide, additional early static imaging cannot be routinely recommended for the assessment of BR in PCa patients.

The new minigastrin analog DOTA-MGS5 is a promising new candidate for targeting cholecystokinin-2 receptor (CCK2R)-expressing tumors. To enable the clinical translation of PET/CT imaging using 68 Ga-labeled DOTA-MGS5, different quality and safety aspects need to be considered to comply with the regulatory framework for clinical trial application. The preparation of the radiopharmaceutical was established using a cassette-based automated synthesis unit. Product specifications, including analytical procedures and acceptance criteria, were adopted from Ph. Eur. monographs for other 68 Ga-labeled radiopharmaceuticals. Non-clinical studies included receptor affinity and cell uptake studies using two different CCK2R-expressing cell lines, as well as pharmacokinetic biodistribution studies in BALB/c mice for dosimetry calculations and toxicological studies in Wistar rats. The produced masterbatches fulfilled the defined acceptance criteria. DOTA-MGS5, with confirmed affinity to the CCK2R, showed a high specific cell uptake and no interaction with other receptors in vitro when radiolabeled with gallium-68. Favorable in vivo properties were observed in biodistribution and dosimetry studies. An effective dose of ~0.01 mSv/MBq was estimated for humans utilizing OLINDA/EXM software. A maximum peptide dose of 50 µg was established for the initial clinical dose based on the toxicity study in rats. The standardized production of [ 68 Ga]Ga-DOTA-MGS5 using an automated synthesis module and the performed non-clinical safety studies support a first exploratory clinical trial with this new PET imaging agent.

Peptide receptor radionuclide therapy (PRRT) has been recognized as a promising therapy against neuroendocrine tumors (NETs). The use of 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) in NETs has been a matter of controversy. The purpose of this study was to evaluate the long-term survival and efficacy of a second PRRT course with 177 Lu-DOTATE in patients with advanced gastroenteropancreatic (GEP) NETs. Furthermore, the value of 18 F-FDG PET/CT in these patients was evaluated. 40 patients with GEP NETs who underwent two PRRT courses with 177 Lu-DOTATATE and combined examinations with 68 Ga-DOTA-TOC and 18 F-FDG PET/CT were evaluated. After the second PRRT course, two patients (5.0%) were in partial remission, 21 patients (52.5%) in stable disease and 17 patients (42.5%) had progressive disease. The median overall survival was 122.10 months. After the second PRRT course, the median overall survival was significantly higher ( p = 0.033) in the 18 F-FDG-negative group compared to the 18 F-FDG-positive group (145.50 versus 95.06 months, respectively). The median time to progression was 19.37 months. In conclusion, a second PRRT course with 177 Lu-DOTATE is an effective treatment approach for GEP NET patients with disease progression. A change in 18 F-FDG status after PRRT may predict the disease course and survival. Patients who are 18 F-FDG-negative have a significantly longer overall survival than those who are 18 F-FDG-positive.

Nasopharyngeal cancer (NPC), endemic in Southeast Asia, lacks effective diagnostic and therapeutic strategies. Even in high-income countries the 5-year survival rate for stage IV NPC is less than 40%. Here we report high somatostatin receptor 2 (SSTR2) expression in multiple clinical cohorts comprising 402 primary, locally recurrent and metastatic NPCs. We show that SSTR2 expression is induced by the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) via the NF-κB pathway. Using cell-based and preclinical rodent models, we demonstrate the therapeutic potential of SSTR2 targeting using a cytotoxic drug conjugate, PEN-221, which is found to be superior to FDA-approved SSTR2-binding cytostatic agents. Furthermore, we reveal significant correlation of SSTR expression with increased rates of survival and report in vivo uptake of the SSTR2-binding 68 Ga-DOTA-peptide radioconjugate in PET-CT scanning in a clinical trial of NPC patients (NCT03670342). These findings reveal a key role in EBV-associated NPC for SSTR2 in infection, imaging, targeted therapy and survival.

Purpose: to assess the influence of intravenous hydration and forced diuresis with furosemide in two different dosages (20 vs 40 mg) on the intensity of tracer accumulation in the urinary collection system and on the occurrence of halo artefact surrounding the urinary bladder and kidneys in [ 68 Ga]Ga-PSMA-11-PET/CT scans., Materials and Methods: Comparison of four groups with 50 patients each, receiving different preparation prior to [ 68 Ga]Ga-PSMA-11-PET/CT. Group one, no preparation. Group two, 500 ml sodium chloride administered immediately after tracer injection. Group three, 500 ml sodium chloride and injection of 20 mg furosemide immediately after tracer administration. Group four, 500 ml sodium chloride and injection of 40 mg furosemide immediately after tracer injection. Images were judged visually whether halo artefact was present; semiquantitative measurements were performed with standardised uptake value (SUV)., Results: Halo artefact of the urinary bladder was present in twelve patients without preparation, in eight patients receiving only sodium chloride, in one patient injected with 20 mg furosemide/sodium chloride and in two patients receiving 40 mg furosemide/sodium chloride, showing a median SUV mean in the bladder of 45.8, 14.4, 4.6 and 5.8, respectively. Differences between patient group without preparation and the two groups with furosemide/sodium chloride were statistically significant. Patient groups receiving 20 mg furosemide and 40 mg furosemide did not differ significantly. Renal halo artefacts were observed in 15 patients of group one, in ten patients of group two, in 14 patients of group three and in 14 patients of group four, with corresponding median SUV mean values of 33.9, 32.0, 37.8 and 30.4 (no statistically significant differences)., Conclusion: Performing [ 68 Ga]Ga-PSMA-11-PET/CT, intravenous injection of 20-mg furosemide and 500-ml sodium chloride significantly reduces the number of bladder halo artefacts and intensity of tracer accumulation in the urinary bladder. A total of 40 mg furosemide does not further improve results.

Combined 18 F-fluoro-deoxyglucose ([18F]FDG) positron emission tomography and computed tomography ([18F]FDG-PET/CT) is increasingly used for the diagnostic and therapeutic management of hematologic and non-hematologic malignancies. Here, we describe a unique case of a patient presenting with very severe aplastic anemia and a mediastinal mass showing disseminated hypermetabolic lesions of the bones after receiving granulocyte colony-stimulating factor (G-CSF), highly suspicious for disseminated metastatic lesions. A 71-year-old patient presented with a 3 week history of dyspnea and fatigue. Blood tests showed severe pancytopenia and iliac crest bone marrow biopsy revealed an extensively hypoplastic bone marrow. Diagnostic work-up by histology, conventional cytogenetics and flow cytometry confirmed the diagnosis of very severe aplastic anemia. Besides blood transfusions, the patient was treated with G-CSF. Furthermore, computed tomography revealed a suspect mass in the anterior mediastinum, presenting with moderate glucose metabolism in the subsequent [18F]FDG-PET/CT scan. In addition, multiple disseminated and highly metabolic bone lesions of primarily the ribs were detected, suspicious of malignant bone infiltration. Since physiologic bone marrow activation by G-CSF-stimulation could not be ruled out, G-CSF therapy was interrupted to repeat the PET/CT scan 10 days later. On the second [18F]FDG-PET/CT the moderately hypermetabolic mediastinal mass persisted. However, the initially FDG-avid bone lesions almost completely resolved, rendering the diagnosis of G-CSF-induced bone marrow hypermetabolism very likely without the need for further invasive diagnostic procedures. The mediastinal mass was thereafter histologically verified as thymoma. Interpretation of [18F]FDG-PET/CT in patients with aplastic anemia may be complicated by the frequent therapeutic use of G-CSF. With G-CSF, islets of residual bone marrow activity can be visualized on [18F]FDG-PET/CT images that might be misinterpreted as malignant bone infiltration. Repeating PET/CT scan after G-CSF discontinuation can prevent unnecessary invasive diagnostic procedures in these patients., Competing Interests: Conflict of interest statement: The author(s) declare that there is no conflict of interest., (© The Author(s), 2020.)

Gastrin-releasing peptide receptors (GRPRs) are potential molecular imaging targets in a variety of tumors. Recently, a 68 Ga-labeled antagonist to GRPRs, NeoBOMB1, was developed for PET. We report on the outcome of a phase I/IIa clinical trial (EudraCT 2016-002053-38) within the EU-FP7 project Closed-loop Molecular Environment for Minimally Invasive Treatment of Patients with Metastatic Gastrointestinal Stromal Tumors ('MITIGATE') (grant agreement no. 602306) in patients with oligometastatic gastrointestinal stromal tumors (GIST). Methods: The main objectives were evaluation of safety, biodistribution, dosimetry, and preliminary tumor targeting of 68 Ga-NeoBOMB1 in patients with advanced tyrosine-kinase inhibitors-treated GIST using PET/CT. Six patients with histologically confirmed GIST and unresectable primary lesion or metastases undergoing an extended protocol for detailed pharmacokinetic analysis were included. 68 Ga-NeoBOMB1 was prepared using a kit procedure with a licensed 68 Ge/ 68 Ga generator. 68 Ga-NeoBOMB1 (3 MBq/kg of body weight) was injected intravenously, and safety parameters were assessed. PET/CT included dynamic imaging at 5, 11, and 19 min as well as static imaging at 1, 2, and 3-4 h after injection for dosimetry calculations. Venous blood samples and urine were collected for pharmacokinetic analysis. Tumor targeting was assessed on a per-lesion and per-patient basis. Results: 68 Ga-NeoBOMB1 (50 μg) was prepared with high radiochemical purity (yield > 97%). Patients received 174 ± 28 MBq of the radiotracer, which was well tolerated in all patients over a follow-up period of 4 wk. Dosimetry calculations revealed a mean effective dose of 0.029 ± 0.06 mSv/MBq, with the highest organ dose to the pancreas (0.274 ± 0.099 mSv/MBq). Mean plasma half-life was 27.3 min with primarily renal clearance (mean 25.7% ± 5.4% of injected dose 4 h after injection). Plasma metabolite analyses revealed high stability; metabolites were detected only in the urine. In 3 patients, a significant uptake with increasing maximum SUVs (SUV max at 2 h after injection: 4.3-25.9) over time was found in tumor lesions. Conclusion: This phase I/IIa study provides safety data for 68 Ga-NeoBOMB1, a promising radiopharmaceutical for targeting GRPR-expressing tumors. Safety profiles and pharmacokinetics are suitable for PET imaging, and absorbed dose estimates are comparable to those of other 68 Ga-labeled radiopharmaceuticals used in clinical routine., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Contrast-enhanced high-resolution computed tomography (contrast-CT) is a standard imaging modality following primary concurrent radiochemotherapy (RCT) for response evaluation in patients with head and neck squamous cell carcinoma (HNSCC). We investigated the additional benefit of Fluorine-18-fluorodeoxyglucose ([18F]FDG) - positron emission tomography with computed tomography (PET-CT), if complete response (CR) in the neck based on contrast-CT was considered unsafe by the interdisciplinary tumor board (ITB)., Methods: In a retrospective observational study, patients recorded in the institutional tumor registry with incident advanced HNSCC following first line treatment with RCT were eligible. If contrast-CT results of the neck were equivocal or positive at response evaluation, a neck dissection (ND) was scheduled. While waiting for the ND, a [18F]FDG-PET-CT was performed in addition. The histopathological outcome of ND served as reference criterion. Accuracy parameters including sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) for both, contrast-CT and PET-CT, served as main outcome parameters., Results: A total of 41 HNSCC patients with positive or equivocal posttreatment contrast-CT were eligible for post-RCT-ND. Of these, 33 received an additional [18F]FDG-PET-CT prior to surgery. Median interval between completion of RCT and the ([18F]FDG)-PET-CT was 10 weeks. Vital persistent tumor in the neck was histopathologically found in 13 of 33 patients with positive or equivocal posttreatment contrast-CT. For contrast-CT and [18F]FDG-PET-CT, sensitivity was 92.3 and 69.2% and did not differ statistically significantly (p = 0.250) whereas specificity was significantly higher for [18F]FDG-PET-CT compared with contrast-CT (80% vs. 25%, p = 0.001). For contrast-CT and [18F]FDG-PET-CT accuracy, PPV and NPV was 31.7, 12.0,96.7 and 78.9, 27.8,95.0%, respectively., Conclusion: A negative [18F]FDG-PET-CT did not improve the exclusion of persistent vital tumor in the neck after primary RCT in comparison with contrast-CT alone. However, a positive [18F]FDG-PET-CT was a considerably better indicator of persistent, vital tumor in the neck than contrast-CT. If, based on the [18F]FDG-PET-CT result, the ND in patients with an uncertain or positive neck response in contrast CT had been omitted, the treatment of persistent nodal disease would have been delayed in 3 of 13 patients. On the other hand, if ND would have only been performed in [18F]FDG-PET-CT positive patients, an unnecessary ND would have been avoided in 11 of 20 patients.