Renal Involvement of Immunoglobulin G4-Related Disease Presenting as a Solitary Hypermetabolic Mass Mimicking Renal Tumor on 18 F-FDG PET/CT.

ABSTRACT: A 62-year-old woman with a 5-year history of diabetes insipidus was found with a solitary renal mass in contrast-enhanced CT. 18 F-FDG PET/CT showed a hypermetabolic mass in the right kidney. Besides, there was increased uptake in the pituitary stalk. The histopathological examination of renal biopsy confirmed the diagnosis of immunoglobulin G4-related disease. After treatment with prednisone and cyclophosphamide, there was obvious radiographic improvement of the renal lesion.

Dynamic PET/CT scan of 68Ga-FAPI-04 for the optimal acquisition time in suspected malignant hepatic cancer patients.

PURPOSE: Dynamic PET/CT scan of 68Ga-FAPI-04 in patients with suspected malignant hepatic lesions were retrospectively analyzed to find the optimal acquisition time with better lesion detection rate. METHODS: Twenty-two patients with lesions confirmed by CT or MRI were performed with dynamic 68Ga-FAPI-04 PET/CT scan. Tracer uptake of lesions and normal organs at different time points were analyzed. Standardized uptake value (SUV) and tumor-to-background (TBR) were calculated based on the quantification of images. RESULTS: SUV of normal organs decreased rapidly from 10 to 30 min and decreased gradually from 30 to 60 min. Besides, the uterus showed a particularly high uptake in all patients (12.62 ± 4.58 at 10 min p.i., 12.04 ± 3.99 at 30 min p.i., 10.92 ± 2.38 at 60 min p.i.). SUV of lesions decreased gradually, while TBR increased from 10- to 60-min post-injection. Visual analysis verified a comparable lesion detectability of 30 min and 60 min with images of 10 min showing a decreased lesion detection number. CONCLUSION: This study revealed that similar detection rates were achieved at both 30 and 60 min, suggesting a static scan at 30 min to be appropriate in the clinic. Besides, although with high lesion uptake, early 68Ga-FAPI-04 PET imaging at 10 min after tracer injection could cause missed lesion detection.

Development and comparison of three 89Zr-labeled anti-CLDN18.2 antibodies to noninvasively evaluate CLDN18.2 expression in gastric cancer: a preclinical study.

BACKGROUND: Isoform 2 of claudin 18 (CLDN18.2) is overexpressed in gastric cancer and may be a promising imaging target. In this study, we constructed three anti-CLDN18.2 antibodies and compared them in preclinical experiments. METHODS: Screening from anti-CLDN18.2 nanobody library, we constructed three antibodies, anti-CLDN18.2 VHH (recombinant single-chain antibody fused with poly-histidine-tag), anti-CLDN18.2 VHH-ABD (recombinant single-chain antibody fused fused with albumin binding domain), and anti-CLDN18.2 VHH-Fc (recombinant single-chain antibody fused with IgG1-Fc) and radiolabeled with 89Zr. Affinity assay, in vitro stability, immunoactivity, blood pharmacokinetics, in vivo and ex vivo biodistribution study, specificity study, and immunohistochemical analysis were performed to assess these radiotracers. RESULTS: The EC50 were 12.21 nM, 2.48 nM, and 0.14 nM for anti-CLDN18.2 VHH, anti-CLDN18.2 VHH-ABD, and anti-CLDN18.2 VHH-Fc, respectively. 89Zr-anti-CLDN18.2 VHH demonstrated the lowest tumor uptake in PET imaging. Both 89Zr-anti-CLDN18.2 VHH-ABD and 89Zr-anti-CLDN18.2 VHH-Fc demonstrated high tumor accumulation, with highest ID%/g of 25.78 ± 5.60 at 24 h post-injection with 89Zr-anti-CLDN18.2 VHH-ABD and 49.43 ± 9.86 at 72 h post-injection with 89Zr-anti-CLDN18.2 VHH-Fc. The specificity of 89Zr-anti-CLDN18.2 VHH-Fc targeting CLDN18.2 was further confirmed by blocking study. The ex vivo biodistribution results were consistent with in vivo biodistribution data. For 89Zr-anti-CLDN18.2 VHH-ABD, tumor uptake was 21.46 ± 1.78 ID%/g at 12 h and 13.73 ± 2.22 ID%/g at 108 h. For 89Zr-anti-CLDN18.2 VHH-Fc, the tumor accumulation was 25.28 ± 3.83 ID%/g at 12 h and 40.13 ± 9.50 ID%/g at 108 h. Immunohistochemistry of the xenograft tissue revealed high and homogenous CLDN18.2 expression in CO-SNU620 tumor. CONCLUSION: Both anti-CLDN18.2 VHH-ABD and anti-CLDN18.2 VHH-Fc can be efficiently and stably radiolabeled with 89Zr for noninvasive imaging and quantification of CLDN18.2 expression in gastric cancer, of which 89Zr-anti-CLDN18.2 VHH-ABD seems to be the optimal choice balancing tumor uptake and liver background. They can provide essential information to select patients who are likely to benefit from CLDN18.2-targeted treatment.

Increased Activity Due to Fractures Does Not Significantly Affect the Accuracy of 68Ga-DOTATATE PET/CT in the Detection of Culprit Tumor in the Evaluation of Tumor-Induced Osteomalacia.

OBJECTIVE: Ga-DOTATATE PET/CT is currently the most common imaging modality in localizing culprit tumors, which can result in tumor-induced osteomalacia (TIO). Fracture, which is one of the most common consequences of the TIO, can also lead to increased Ga-DOTATATE activity and potentially affect the accuracy of Ga-DOTATATE PET/CT imaging. The aim of this investigation is to evaluate whether the increased Ga-DOTATATE activity at the sites of the fracture will cause interpretation difficulty in the localizing the culprit tumor causing TIO. METHOD: The images of Ga-DOTATATE PET/CT scan from a total of 54 patients who had multiple foci of increased Ga-DOTATATE PET/CT on PET/CT were retrospectively analyzed. Not only was the intensity of the activity on PET but also the appearance of the activity on CT taken into consideration when the interpretation of the images occurred. The results from imaging analysis were compared with the clinical chart record. All patients had tentative clinical diagnosis of TIO. RESULTS: The causative tumors in 53 patients were eventually identified. In 1 patient, the causative tumor was not identified. Among the 53 patients with confirmed TIO, 52 tumors were accurately localized. CONCLUSIONS: Mild activity at the sites of fracture is not a major challenging factor in the interpretation of Ga-DOTATATE PET/CT in the evaluation of TIO when both intensity on PET and morphology on CT were assessed.

miR-125b is downregulated in systemic lupus erythematosus patients and inhibits autophagy by targeting UVRAG.

Systemic lupus erythematosus (SLE) is a severe autoimmune disease and the pathogenesis remains incompletely understood. This study aimed to investigate the role of miR-125b in the pathogenesis of SLE and explore the underlying mechanism. Compared to healthy controls, the expression of miR-125b decreased in peripheral blood mononuclear cells (PBMCs) of SLE patients. In addition, PBMCs exposed to ultraviolet B had lower miR-125b level compared to those unexposed to radiation. We identified UV radiation resistance associated gene (UVRAG) as a target of miR-125b. Jurkat cells treated with miR-125b-5p agomir showed reduced levels of ATG7, Beclin-1 and LC3 II and decreased autophagy. In contrast, Jurkat cells treated with miR-125b-5p antagomir showed increased levels of ATG7, Beclin-1 and LC3 II and increased autophagy. Furthermore, Jurkat cells transfected with UVRAG expression vector showed higher expression of ATG7, Beclin-1 and LC3 II and increased autophagy. Conversely, cells transfected with UVRAG siRNA had lower expression of ATG7, Beclin-1 and LC3 II and decreased autophagy. Taken together, our data demonstrate that Ultraviolet B radiation can downregulate miR-125b-5p and increase UVRAG expression and autophagy activity in PBMCs of SLE patients. These findings help explain how ultraviolet B exacerbates SLE and suggest that UVRAG is a potential therapeutic target for SLE.

Comparison among Reconstruction Algorithms for Quantitative Analysis of 11C-Acetate Cardiac PET Imaging.

Objective: Kinetic modeling of dynamic 11C-acetate PET imaging provides quantitative information for myocardium assessment. The quality and quantitation of PET images are known to be dependent on PET reconstruction methods. This study aims to investigate the impacts of reconstruction algorithms on the quantitative analysis of dynamic 11C-acetate cardiac PET imaging. Methods: Suspected alcoholic cardiomyopathy patients (N = 24) underwent 11C-acetate dynamic PET imaging after low dose CT scan. PET images were reconstructed using four algorithms: filtered backprojection (FBP), ordered subsets expectation maximization (OSEM), OSEM with time-of-flight (TOF), and OSEM with both time-of-flight and point-spread-function (TPSF). Standardized uptake values (SUVs) at different time points were compared among images reconstructed using the four algorithms. Time-activity curves (TACs) in myocardium and blood pools of ventricles were generated from the dynamic image series. Kinetic parameters K1 and k2 were derived using a 1-tissue-compartment model for kinetic modeling of cardiac flow from 11C-acetate PET images. Results: Significant image quality improvement was found in the images reconstructed using iterative OSEM-type algorithms (OSME, TOF, and TPSF) compared with FBP. However, no statistical differences in SUVs were observed among the four reconstruction methods at the selected time points. Kinetic parameters K1 and k2 also exhibited no statistical difference among the four reconstruction algorithms in terms of mean value and standard deviation. However, for the correlation analysis, OSEM reconstruction presented relatively higher residual in correlation with FBP reconstruction compared with TOF and TPSF reconstruction, and TOF and TPSF reconstruction were highly correlated with each other. Conclusion: All the tested reconstruction algorithms performed similarly for quantitative analysis of 11C-acetate cardiac PET imaging. TOF and TPSF yielded highly consistent kinetic parameter results with superior image quality compared with FBP. OSEM was relatively less reliable. Both TOF and TPSF were recommended for cardiac 11C-acetate kinetic analysis.

Preclinical PET imaging of HIP/PAP using 1'-18F-fluoroethyl-ß-D-lactose.

PURPOSE: This study aims at preclinical evaluation of a recently reported lactose analogue, 1'-18F-fluoroethyl-ß-D-lactose (18F-FEL), in binding to hepatocarcinoma-intestine-pancreas and pancreatitis-associated protein (HIP/PAP) in vitro and in vivo. METHODS: In this study, a multifunctional module was employed for the automated synthesis of 18F-FEL. Additional radiochemical purity, biodistribution, in vitro and in vivo competition, metabolic stability and micro-PET studies were performed using T3M4 and SK-BR-3 xenografts. Expression of HIP/PAP in T3M4 and SK-BR-3 tumor sections and cell lines were tested with immunohistochemistry (IHC) and western blot analysis. RESULTS: The synthesis of 18F-FEL was completed in 30 min, with a radiochemical yield of 20 ± 5% and specific activity of 14.2 ± 7.1 GBq/µmol. 18F-FEL exhibited high HIP/PAP-binding affinity with a half maximal inhibitory concentration (IC50) of 22.0 ± 4.0 nM. 18F-FEL demonstrated high stability and specific tumor accumulation, which was reduced by approximately 80% in a PET competition assay by co-injection of ß-D-lactose. High expression of HIP/PAP was detected in T3M4 tumors and cell line, but negative result was found for SK-BR-3 cell line. CONCLUSION: 18F-FEL has a high binding property to HIP/PAP, high stability and excellent pharmacokinetics in vivo and therefore warrants further evaluation in a proof-of-concept study in humans.

Acinar cell carcinoma of the pancreas presenting as diffuse pancreatic enlargement: Two case reports and literature review.

RATIONALE: Pancreatic acinar cell carcinoma (ACC) is a rare malignant tumor of exocrine pancreas. It is typically a well-marginated large solid mass arising in a certain aspect of the pancreas. Diffuse involvement of ACC in the pancreas is very rare, and may simulate pancreatitis in radiological findings. We report 2 cases of ACC presenting as diffuse enlargement of the pancreas due to tumor involvement without formation of a distinct mass. PATIENT CONCERNS: The patients consisted of a 41-year-old man with weight loss and a 77-year-old man who was asymptomatic. DIAGNOSES: Computed tomography (CT) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT showed diffuse enlargement of the pancreas forming a sausage-like shape with homogenously increased FDG activity. INTERVENTIONS: Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) biopsy of the pancreatic lesion was performed. OUTCOMES: Histopathology results from the pancreas confirmed the diagnosis of pancreatic ACC. LESSONS: Because diffuse enlargement of the pancreas is a common imaging feature of pancreatitis, recognition of this rare morphologic pattern of ACC is important for radiological diagnosis of this tumor.

Solitary Plasmacytoma in the Renal Pelvis on 18F-FDG and 11C-Acetate PET/CT.

A 70-year-old man was incidentally found to have an occupying lesion in the left renal pelvis by ultrasonography during a routine health examination. CT images suggested renal cell carcinoma. FDG PET/CT scan was acquired for staging. The images did not reveal any hypermetabolic metastases. However, the metabolic activity of the lesion in the right renal pelvis was not unambiguously determined because of interference of radioactive urine. C-acetate PET/CT, on the other hand, clearly revealed increased activity in the left renal pelvis. Pathological examination demonstrated solitary extraosseous plasmacytoma.