PurposeIgG4-related disease (IgG4-RD) is an increasingly recognized clinicopathological disorder with immune-mediated inflammatory lesions mimicking malignancies. A cohort study was prospectively designed to investigate the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in characterizing IgG4-RD.MethodsThirty-five patients diagnosed with IgG4-RD according to the consensus criteria were enrolled with informed consent. All patients underwent baseline 18F-FDG PET/CT evaluation. Among them, 29 patients underwent a second 18F-FDG PET/CT scan after 2 to 4 weeks of steroid-based therapy.ResultsAll 35 patients were found with 18F-FDG-avid hypermetabolic lesion(s); 97.1 % (34/35) of these patients showed multi-organ involvement. Among the 35 patients, 71.4 % (25/35) patients were found with more organ involvement on 18F-FDG PET/CT than conventional evaluations including physical examination, ultrasonography, and computed tomography (CT). 18F-FDG PET/CT demonstrated specific image characteristics and pattern of IgG4-RD, including diffusely elevated 18F-FDG uptake in the pancreas and salivary glands, patchy lesions in the retroperitoneal region and vascular wall, and multi-organ involvement that cannot be interpreted as metastasis. Comprehensive understanding of all involvement aided the biopsy-site selection in seven patients and the recanalization of ureteral obstruction in five patients. After 2 to 4 weeks of steroid-based therapy at 40 mg to 50 mg prednisone per day, 72.4 % (21/29) of the patients showed complete remission, whereas the others exhibited > 81.8 % decrease in 18F-FDG uptake.ConclusionF-FDG PET/CT is a useful tool for assessing organ involvement, monitoring therapeutic response, and guiding interventional treatment of IgG4-RD. The image pattern is suggested to be updated into the consensus diagnostic criteria for IgG4-RD.

Introduction The impact of prior therapies, especially chemotherapy, on overall survival (OS) in patients with castration-resistant prostate cancer (CRPC) receiving [ 177 Lu]Lu-PSMA-617 therapy has been the subject of controversy. Therefore, WARMTH decided to plan a multicenter retrospective analysis (the “617 trial”) to evaluate response rate and OS as well as the impact of prior therapies on OS in more than 300 patients treated with 177 Lu-PSMA-617. Materials and methods The data of 631 metastatic CRPC (mCRPC) patients from 11 different clinics were evaluated. According to the inclusion and exclusion criteria, all patients had to have received at least abiraterone or enzalutamide prior to [ 177 Lu]Lu-PSMA-617 therapy. The patients were divided into three groups: patients who had received prior chemotherapy, patients who avoided chemotherapy, and patients for whom a chemotherapy was contraindicated. Results The analysis included the data of 416 patients, with a median age of 71.9 years. At the time of analysis, 87 patients (20,9%) were still alive. A total of 53.6% of patients had received both abiraterone and enzalutamide; 75.5% and 26.4% had a history of chemotherapy with docetaxel and cabazitaxel, respectively. A total of 20.4% had had Ra-223. The median OS was 11.1 months. Prior chemotherapy, the existence of bone and liver metastases, as well as Eastern Cooperative Oncology Group (ECOG) status, were significant prognosticators of worse overall survival in both univariate and multivariate analyses. Patients without any prior chemotherapy showed a significantly longer OS (14.6 months). The median OS in patients who received one or two lines of chemotherapy with docetaxel or docetaxel followed by cabazitaxel, respectively, was 10.9 months and 8.9 months. There was no difference in OS between patients who had not received chemotherapy and patients for whom chemotherapy was contraindicated. The other prior therapies did not have any significant impact on OS. Conclusion In the present multicenter analysis, chemotherapy-naïve mCRPC patients receiving [ 177 Lu]Lu-PSMA-617 therapy had a significantly longer OS than patients with a history of chemotherapy. This remained independent in the multivariate analysis besides presence of bone and liver metastases as negative prognosticators for survival, whereas an ECOG of 0–1 is associated with a longer OS. Electronic supplementary material The online version of this article (10.1007/s00259-020-04797-9) contains supplementary material, which is available to authorized users.

Fibroblast activation protein (FAP) is a promising target for diagnosis and therapy of numerous malignant tumors. FAP-2286 is the conjugate of a FAP-binding peptide, which can be labeled with radionuclides for theranostic applications. We present the first-in-human results using 177 Lu-FAP-2286 for peptide-targeted radionuclide therapy (PTRT). Methods: PTRT using 177 Lu-FAP-2286 was performed in 11 patients with advanced adenocarcinomas of pancreas, breast, rectum and ovary after prior confirmation of uptake on 68 Ga-FAP-2286/-FAPI-04-PET/CT.Results: Administration of 177 Lu-FAP-2286 (5.8 ± 2.0 GBq; range, 2.4-9.9 GBq) was well tolerated, with no adverse symptoms or clinically detectable pharmacologic effects being noticed or reported in any of the patients. The whole-body effective doses were 0.07 ± 0.02 Gy/GBq (range 0.04 -0.1). The mean absorbed doses for kidneys and red marrow were 1.0 ± 0.6 Gy/GBq (range 0.4 -2.0) and 0.05 ± 0.02 Gy/GBq (range 0.03 -0.09), respectively. Significant uptake and long tumor retention of 177 Lu-FAP-2286 resulted in high absorbed tumor doses, e.g., 3.0 ± 2.7 Gy/GBq (range 0.5 -10.6) in bone metastases. No grade (G) 4 adverse events were observed. G3 events occurred in 3 patients -1 pancytopenia, 1 leukocytopenia and 1 pain flareup; 3 patients reported pain-response. Conclusions: 177 Lu-FAP-2286 PTRT, applied in a broad spectrum of cancers, was relatively well-tolerated with acceptable side effects and demonstrated long retention of the radiopeptide. Prospective clinical studies are warranted.

To date, limited data are available concerning peptide receptor radionuclide therapy (PRRT) of grade 3 (G3) neuroendocrine neoplasms (NENs) with a Ki-67 proliferation index of >20%. The purpose of this study was to analyze the long-term outcome, efficacy and safety of PRRT in patients with SSTR-expressing G3 NEN. A total of 69 patients (M=41 males; age 28-81 years) received PRRT with lutetium-177 (Lu) and/or yttium-90 (Y) labeled somatostatin analogs (DOTATATE or DOTATOC). Twenty-two patients had radiosensitising chemotherapy. Kaplan-Meier analysis was performed to calculate progression-free survival (PFS) and overall survival (OS), defined from start of PRRT, including a subgroup analysis for patients with a Ki-67 of ≤55% and >55%. Treatment response was evaluated according to RECIST 1.1 as well as by molecular imaging criteria (EORTC). Short and long-term toxicity was documented (CTCAE v.5.0) using a structured database (comprising over 250 items per patient) and retrospectively analyzed. Forty-six patients had pancreatic, 11 CUP, 6 midgut, 3gastric, and 3 rectal NEN. Median follow-up was 94.3 months. The median PFS was 9.6 months and median OS was 19.9 months. For G3 NEN with a Ki-67 ≤55% ( = 53), the median PFS was 11 months and median OS 22 months. Patients with a Ki-67 >55% ( = 11), had a median PFS of 4 months and a median OS of 7 months. For those patients with positive SSTR imaging, but no FDG uptake, the median PFS was 24 months and median OS was 42 months. A significant difference was found for both, PFS and OS, with a median PFS of 16 vs 5 months and a median OS of 27 vs 9 months for a SUV >15.0 and a SUV ≤15.0 on SSTR-PET, respectively. In the group with FDG scored as 3-4, the median PFS was 7.1 months and the median OS 17.2 months. For FDG scored as 0-2, the median PFS was 24.3 months and the median OS 41.6 months. PRRT was well-tolerated by all patients; no grade 3 or grade 4 hematotoxicity occurred and no clinically significant decline in renal function was observed. There was no hepatotoxicity. PRRT was tolerated well without significant adverse effects and is efficacious in G3 NEN with promising clinical outcome, especially in patients with a Ki-67 index of ≤55% and even in patients who have failed chemotherapy. Baseline FDG along with SSTR molecular imaging is useful to stratify those G3-NEN patients with high uptake on SSTR PET/CT and no or minor FDG-avidity, a mismatch pattern which is associated with a better long term prognosis.

This work was designed to study the safety, biodistribution, and radiation dosimetry of a gastrin-releasing peptide receptor (GRPR)– targeting, 68Ga-labeled bombesin (BBN) peptide derivative PET tracer, NOTA-Aca-BBN(7–14) (denoted as 68Ga-BBN) in healthy volunteers and to assess the level of receptor expression in glioma patients. Methods Four healthy volunteers (2 male and 2 female) underwent whole-body PET/CT at multiple time points after a bolus injection of 68Ga-BBN (111 ± 148 MBq). Regions of interest were drawn manually over major organs, and time–activity curves were obtained. Dosimetry was calculated using the OLINDA/EXM software. Twelve patients with glioma diagnosed by contrast-enhanced MRI underwent PET/CT at 30–45 min after 68Ga-BBN injection. Within 1 wk afterward, the tumor was surgically removed and immunohistochemical staining of tumor samples against GRPR was performed and correlated with the PET/CT results. Results 68Ga-BBN was well tolerated in all healthy volunteers, with no adverse symptoms being noticed or reported. 68Ga-BBN cleared rapidly from the circulation and was excreted mainly through the kidneys and urinary tract. The total effective dose equivalent and effective dose were 0.0335 ± 0.0079 and 0.0276 ± 0.0066 mSv/MBq, respectively. In glioma patients, all MRI-identified lesions showed high signal intensity on 68Ga-BBN PET/CT. SUVmax and SUVmean were 2.08 ± 0.58 and 1.32 ± 0.37, respectively. With normal brain tissue as background, tumor-to-background ratios were 24.0 ± 8.85 and 13.4 ± 4.54 based on SUVmax and SUVmean, respectively. The immunohistochemical staining confirmed a positive correlation between SUV and GRPR expression level (r2 = 0.71, P < 0.001). Conclusion 68Ga-BBN is a PET tracer with favorable pharmacokinetics and a favorable dosimetry profile. It has the potential to evaluate GRPR expression in glioma patients and guide GRPR-targeted therapy of glioma.

Suitably labeled Evans blue dye has been successfully applied to evaluate cardiac function, vascular permeability, and lymphatic imaging in preclinical settings. This study documented the first-inhuman application of 68Ga-1,4,7-triazacyclononane-N,N′,N″-triacetic acid (NOTA)-NEB. Methods The NOTA-conjugated truncated form of Evans blue, NEB, was labeled with 68Ga and tested in BALB/C mice for dynamic PET and ex vivo biodistribution studies. Three healthy volunteers (2 men and 1 woman) underwent 90-min whole-body dynamic PET. The absorbed doses for major organs and whole body were calculated using OLINDA/EXM software. Eleven patients with focal hepatic lesions diagnosed by enhanced CT or MR imaging were subjected to whole-body PET/CT acquisitions at 30 min after intravenous injection of 111–148 MBq (3–4 mCi) of 68Ga-NEB. Results NEB dye was labeled with 68Ga (half-time, 68 min) with high yield and purity. After intravenous injection, 68Ga-NEB formed a complex with serum albumin, thus most of the radioactivity was retained in blood circulation. The tracer was demonstrated to be safe in both healthy volunteers and recruited patients without side effects or allergies. Among the 11 patients, hemangiomas showed much higher 68Ga-NEB signal intensity than the surrounding normal hepatic tissues, whereas no apparent difference between lesions and hepatic tissues was identified on 18F-FDG PET. All other focal hepatic lesions including hepatocellular carcinoma, hepatic cysts, and neuroendocrine tumor liver metastases showed negative 68Ga-NEB contrast to hepatic tissues. Conclusion As a blood-pool imaging agent, 68Ga-NEB is safe to use in the clinic, and our preliminary studies demonstrate the value of differentiating hepatic hemangioma from other benign or malignant focal hepatic lesions. Easy labeling with different positron emitters of various half-lives, excellent pharmacokinetics, and imaging quality warrant further clinical applications of NEB-based PET tracers.

Workplace violence in Chinese township hospitals is a major public health problem. We identified the risk factors of healthcare workers’ worry about experiencing workplace violence in 90 Chinese township hospitals and determined specific measures for differing stages of violence (based on crisis management theory). Participants were 440 general practitioners and 398 general nurses from Heilongjiang Province, China (response rate 84.6%). One hundred and six (12.6%) respondents reported being physically attacked in their workplace in the previous 12 months. Regarding psychological violence, the most common type reported was verbal abuse (46.0%). While most (85.2%) respondents had some degree of worry about suffering violence, 22.1% were worried or very worried. Ordinal regression analysis revealed that being ≤35 years of age, having a lower educational level, having less work experience, and working night shifts were all associated with worry about workplace violence. Furthermore, those without experience of such violence were more likely to worry about it. Respondents’ suggested measures for controlling violence included “widening channels on medical dispute solutions,” “improving doctor-patient communication,” and “advocating for respect for medical workers via the media.” Results suggest the target factors for reducing healthcare workers’ worry by according to the type of education and training and possible measures for limiting workplace violence in township hospitals.

Radiolabeled somatostatin analog therapy has become an established treatment method for patients with well to moderately differentiated unresectable or metastatic neuroendocrine tumors (NETs). The most frequently used somatostatin analogs in clinical practice are octreotide and octreotate. However, both peptides showed suboptimal retention within tumors. The aim of this first-in-humans study is to explore the safety and dosimetry of a long-acting radiolabeled somatostatin analog, Lu-1, 4, 7, 10-tetra-azacyclododecane-1, 4, 7, 10-tetraacetic acid-Evans blue-octreotate (Lu-DOTA-EB-TATE). Eight patients (6 men and 2 women; age range, 27-61 y) with advanced metastatic NETs were recruited. Five patients received a single dose, 0.35-0.70 GBq (9.5-18.9 mCi), ofLu-DOTA-EB-TATE and underwent serial whole-body planar and SPECT/CT scans at 2, 24, 72, 120, and 168 h after injection. The other 3 patients received intravenous injection of 0.28-0.41 GBq (7.5-11.1 mCi) of Lu-DOTATATE for the same imaging acquisition procedures at 1, 3, 4, 24, and 72 h after injection. The dosimetry was calculated using the OLINDA/EXM 1.1 software. Administration of Lu-DOTA-EB-TATE was well tolerated, with no adverse symptoms being noticed or reported in any of the patients. Compared withLu-DOTATATE, Lu-DOTA-EB-TATE showed extended circulation in the blood and achieved a 7.9-fold increase of tumor dose delivery. The total-body effective doses were 0.205 ± 0.161 mSv/MBq forLu-DOTA-EB-TATE and 0.174 ± 0.072 mSv/MBq for Lu-DOTATATE. Significant dose delivery increases to the kidneys and bone marrow were also observed in patients receivingLu-DOTA-EB-TATE compared with those receiving Lu-DOTATATE (3.2 and 18.2-fold, respectively). By introducing an albumin-binding moiety, Lu-DOTA-EB-TATE showed remarkably higher uptake and retention in NETs as well as significantly increased accumulation in the kidneys and red marrow. It has great potential to be used in peptide receptor radionuclide therapy for NETs with lower dose and less frequency of administration.