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Introduction: The ability of PET/CT imaging to delineate neuroendocrine neoplasms (NENs) and predict prognosis in affected patients is often compromised by substantial uptake heterogeneity. We hereby proposed a hybrid standardized uptake value (SUV) thresholding algorithm to extract volumetric parameters from somatostatin receptor (SSTR) PET/CT imaging and investigate their prognostic performance in patients with 68Ga-DOTATATE-avid stage IV NENs. Methods: For 38 retrospectively enrolled patients, we used either fixed SUV thresholding of normal liver parenchyma (method A), 41% of the SUVmax for each lesion (method B), or a hybrid method (method A for liver metastases; fixed SUV threshold of normal bone for bone metastases; method B for primary tumors and other metastases) to quantify the whole-body SSTR-expressing tumor volume (SRETVwb) and total lesion SSTR expression (TLSREwb). Patient survival was also recorded and analyzed. Results: PET/CT images revealed heterogeneous uptake of 68Ga-DOTATATE at primary and metastatic sites. Progression-free survival (PFS) and overall survival (OS) were negatively correlated with the extent of liver or bone metastases (p < 0.05), but not significantly correlated with tumor grade or 18F-FDG PET/CT positivity. By the hybrid method, PFS was significantly shorter in patients with high SRETVwb, and OS was significantly shorter in those with high SRETVwb and TLSREwb (p < 0.05). However, when derived from method A or method B, neither SRETVwb nor TLSREwb could predict patient outcomes. Conclusion: Compared with other methods used in 68Ga-DOTATATE-avid stage IV NENs, our hybrid SUV thresholding method demonstrated robustness, with greater precision, reliability, and prognostic power. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the influences of age‐matched control and/or age‐specific template on voxel‐wise analysis of brain 18F‐fluorodeoxyglucose positron emission tomography (18F‐FDG PET) data in pediatric epilepsy patients. We, retrospectively, included 538 pediatric (196 females; age range of 12 months to 18 years) and 35 adult subjects (18 females; age range of 20–50 years) without any cerebral pathology as pediatric and adult control group, respectively, as well as 109 pediatric patients with drug‐resistant epilepsy (38 females; age range of 13 months to 18 years) as epilepsy group. Statistical parametric mapping (SPM) analysis for 18F‐FDG PET data of each epilepsy patients was performed in four types of procedures, by using age‐matched controls with age‐specific template, age‐matched controls with adult template, adult controls with age‐specific template or adult controls with adult template. The numbers of brain regions affected by artifacts among these four types of SPM analysis procedures were further compared. Any template being adopted, the artifacts were significantly less in SPM analysis procedures using age‐matched controls than those using adult controls in each age range (p <.001 in each comparison), except in the age range of 15–18 (p >.05 in each comparison). No significant difference was found in artifacts, when compared procedures using the identical control group with different templates (p = 1.000 in each comparison). In conclusion, the age stratification for age‐matched control should be divided as many layers as possible for the SPM analysis of brain 18F‐FDG PET images, especially in pediatric patients ≤14‐year‐old, while age‐specific template is not mandatory. [ABSTRACT FROM AUTHOR]

Objective: Prostate-specific membrane antigen (PSMA)-PET/CT imaging has gained increasing clinical importance for the detection and staging of high-risk primary prostate cancer (PCa). However, it is unclear whether the routine practice of prostate biopsy obscures the image finding of PSMA-PET/CT. This study aimed to compare the tumor positivity rate of PSMA-PET/CT performed pre- (PSMA-PET/CTpre) and post-biopsy (PSMA-PET/CTpost) in high-risk PCa patients. Patients and methods: We matched 58 PSMA-PET/CTpost with 58 PSMA-PET/CTpre studies for primary detection of high-risk PCa according to clinical characteristics. Three subgroups of PSMA-PET/CTpost were defined by the intervals after biopsy (≤ 1 week, 1 ~ 2 weeks, and 2 ~ 5 weeks). Tumor positivity rates were determined, and SUVmax of primary tumors were compared separately for the two main groups and the related subgroups. Malignant prostate tissues from 20 of these patients were examined by immunohistochemical analysis of PSMA. In addition, the values of PSMA-PET/CTpre and PSMA-PET/CTpost in assessing seminal vesicle invasion (SVI) were evaluated in patients who underwent radical prostatectomy. Results: All the primary tumors were positive on PSMA-PET/CTpost and PSMA-PET/CTpre imaging, resulting in a patient-based positivity rates of 100% (58/58) in both groups. All examined IHC results (20/20) confirmed the high-level expression of PSMA. SUVmax of primary tumors did not differ between the two main groups (16.1, IQR 9.8–26.6 vs. 16.5, IQR 11.0–26.7, p > 0.05). Subgroup analysis of PSMA-PET/CTpost (≤ 1 week, 1 ~ 2 weeks, and 2 ~ 5 weeks) also showed no significant difference in tumor SUVmax (15.8, IQR 9.5–22.2; 17.8, IQR 9.8–29.2; and 15.4, IQR 10.1–30.3. p > 0.05). PSMA-PET/CTpost and PSMA-PET/CTpre exhibited similar value in SVI detection as well. Conclusions: The tumor positivity rate was consistently high for PSMA-PET/CT pre- and post-biopsy. A prior biopsy does not seem to affect the tumor positivity rate of PSMA-PET/CT in high-risk PCa. [ABSTRACT FROM AUTHOR]

Purpose: Tumor microenvironment immune types (TMITs) are closely related to the efficacy of immunotherapy. We aimed to assess the predictive ability of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)-based radiomics of TMITs in treatment-naive patients with non-small cell lung cancer (NSCLC). Methods: A retrospective analysis was performed in 103 patients with NSCLC who underwent 18F-FDG PET/CT scans. The patients were randomly assigned into a training set (n = 71) and a validation set (n = 32). Tumor specimens were analyzed by immunohistochemistry for the expression of programmed death-ligand 1 (PD-L1), programmed death-1 (PD-1), and CD8+ tumor-infiltrating lymphocytes (TILs) and categorized into four TMITs according to their expression of PD-L1 and CD8+ TILs. LIFEx package was used to extract radiomic features. The optimal features were selected using the least absolute shrinkage and selection operator (LASSO) algorithm, and a radiomics signature score (rad-score) was developed. We constructed a combined model based on the clinical variables and radiomics signature and compared the predictive performance of models using receiver operating characteristic (ROC) curves. Results: Four radiomic features (GLRLM_LRHGE, GLZLM_SZE, SUVmax, NGLDM_Contrast) were selected to build the rad-score. The rad-score showed a significant ability to discriminate between TMITs in both sets (p < 0.001, p < 0.019), with an area under the ROC curve (AUC) of 0.800 [95% CI (0.688–0.885)] in the training set and that of 0.794 [95% CI (0.615–0.916)] in the validation set, while the AUC values of clinical variables were 0.738 and 0.699, respectively. When clinical variables and radiomics signature were combined, the complex model showed better performance in predicting TMIT-I tumors, with the AUC values increased to 0.838 [95% CI (0.731–0.914)] in the training set and 0.811 [95% CI (0.634–0.927)] in the validation set. Conclusion: The FDG-PET/CT-based radiomic features showed good performance in predicting TMIT-I tumors in NSCLC, providing a promising approach for the choice of immunotherapy in a clinical setting. [ABSTRACT FROM AUTHOR]

Purpose: Dual-time-point 18F-fluorodeoxyglucose positron emission tomography (DTP 18F-FDG PET), which reflects the dynamics of tumor glucose metabolism, may also provide a novel approach to the characterization of both cancer cells and immune cells within the tumor immune microenvironment (TIME). We investigated the correlations between the metabolic parameters (MPs) of DTP 18F-FDG PET images and the tumor microenvironment immune types (TMITs) in patients with non-small cell lung cancer (NSCLC). Methods: A retrospective analysis was performed in 91 patients with NSCLC who underwent preoperative DTP 18F-FDG PET/CT scans. MPs in the early scan (eSUVmax, eSUVmean, eMTV, eTLG) and delayed scan (dSUVmax, dSUVmean, dMTV, dTLG) were calculated, respectively. The change in MPs (ΔSUVmax, ΔSUVmean, ΔMTV, ΔTLG) between the two time points were calculated. Tumor specimens were analyzed by immunohistochemistry for PD-1/PD-L1 expression and CD8+ tumor-infiltrating lymphocytes (TILs). TIME was classified into four immune types (TMIT I ~ IV) according to the expression of PD-L1 and CD8+ TILs. Correlations between MPs with TMITs and the immune-related biomarkers were analyzed. A composite metabolic signature (Meta-Sig) and a combined model of Meta-Sig and clinical factors were constructed to predict patients with TMIT I tumors. Results: eSUVmax, eSUVmean, dSUVmax, dSUVmean, ΔSUVmax, ΔSUVmean, and ΔTLG were significantly higher in PD-L1 positive patients (p = 0.0007, 0.0006, < 0.0001, < 0.0001, 0.0002, 0.0002, 0.0247, respectively), and in TMIT-I tumors (p = 0.0001, < 0.0001, < 0.0001, < 0.0001, 0.0009, 0.0009, 0.0144, respectively). Compared to stand-alone MP, the Meta-Sig and combined model displayed better performance for assessing TMIT-I tumors (Meta-sig: AUC = 0.818, sensitivity = 86.36%, specificity = 73.91%; Model: AUC = 0.869, sensitivity = 77.27%, specificity = 82.61%). Conclusion: High glucose metabolism on DTP 18F-FDG PET correlated with the TMIT-I tumors, and the Meta-Sig and combined model based on clinical and metabolic information could improve the performance of identifying the patients who may respond to immunotherapy. [ABSTRACT FROM AUTHOR]

Integration of non-vascularized bone grafting and bone marrow aspirate infusion in transplantation may provide clinical benefit. Here we have incorporated bone fragment co-transplantation and bone marrow aspirate infusion (BF-BM) into living kidney transplantation (LKT). Twenty LKT recipients receiving bone fragments and bone marrow aspirates donated from their corresponding donors were enrolled into a retrospective study. A contemporaneous control group was formed of 38 out of 128 conventional LKT recipients, selected using propensity score matching by a 1:2 Greedy algorithm. Ultrasonography, contrast-enhanced ultrasonography (US/CEUS) and SPECT/CT showed that the co-transplanted bone fragments remained viable for 6 months, subsequently shrank, and finally degenerated 10 months post-transplantation. BF-BM resulted in earlier kidney recovery and more robust long-term kidney function. Throughout 5 years of follow-up, BF-BM had regulatory effects on dendritic cells (DCs), T helper (Th1/Th2) cells and regulatory T cells (Tregs). Both alloantigen-specific lymphocyte proliferation and panel reactive antibody levels were negative in all recipients with or without BF-BM. In addition, the BF-BM group experienced few complications during the 5-year follow-up (as did the donors)—this was not different from the controls. In conclusion, BF-BM is safe and benefits recipients by protecting the kidney and regulating the immune response. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) imaging plays an indispensable role in early disease detection and postoperative patient staging diagnosis. However, PET imaging requires not only additional computed tomography (CT) imaging to provide detailed anatomical information but also attenuation correction (AC) maps calculated from CT images for precise PET quantification, which inevitably demands that patients undergo additional doses of ionizing radiation. To reduce the radiation dose and simultaneously obtain high-quality PET/CT images, in this work, we present an alternative based on deep learning that can estimate synthetic attenuation corrected PET (sAC PET) and synthetic CT (sCT) images from non-attenuation corrected PET (NAC PET) scans for whole-body PET/CT imaging. Our model consists of two stages: the first stage removes noise and artefacts in the NAC PET images to generate sAC PET images, and the second stage synthesizes CT images from the sAC PET images obtained in the first stage. Both stages employ the same deep Wasserstein generative adversarial network and identical loss functions, which encourage the proposed model to generate more realistic and satisfying output images. To evaluate the performance of the proposed algorithm, we conducted a comprehensive study on a total of 45 sets of paired PET/CT images of clinical patients. The final experimental results demonstrated that both the generated sAC PET and sCT images showed great similarity to true AC PET and true CT images based on both qualitative and quantitative analyses. These results also indicate that in the future, our proposed algorithm has tremendous potential for reducing the need for additional anatomic imaging in hybrid PET/CT systems or the need for lengthy MR sequence acquisition in hybrid PET/MRI systems. [ABSTRACT FROM AUTHOR]

Clinical PET/CT examinations rely on CT modality for anatomical localization and attenuation correction of the PET data. However, the use of CT significantly increases the risk of ionizing radiation exposure for patients. We propose a deep learning framework to learn the relationship mapping between attenuation corrected (AC) PET and non-attenuation corrected (NAC) PET images to estimate PET attenuation maps and generate pseudo-CT images for medical observation. In this study, 5760, 1608 and 1351 pairs of transverse PET-CT slices were used as the training, validation, and testing sets, respectively, to implement the proposed framework. A pix2pix model was adopted to predict AC PET images from NAC PET images, which allowed the calculation of PET attenuation maps (µ-maps). The same model was then applied to generate realistic CT images from the calculated µ-maps. The quality of predicted AC PET and CT was assessed using normalized root mean square error (NRMSE), peak signal-to-noise ratio (PSNR), structural similarity index (SSIM) and Pearson correlation coefficient (PCC). Relative to true AC PET, the synthetic AC PET achieved superior quantitative performances with 2.20 ± 1.17% NRMSE, 34.03 ± 4.73 dB PSNR, 97.90 ± 1.22% SSIM and 98.45 ± 1.31% PCC. The synthetic CT and synthetic AC PET images were deemed acceptable by radiologists who rated the images, as they provided sufficient anatomical and functional information, respectively. This work demonstrates that the proposed deep learning framework is a promising method in clinical applications, such as radiotherapy and low-dose imaging. [ABSTRACT FROM AUTHOR]

Rationale: The role of oxidative stress metabolism during hepatocellular carcinoma (HCC) formation potentially allows for positron emission tomography (PET) imaging of oxidative stress activity for early and precise HCC detection. However, there is currently limited data available on oxidative-stress-related PET imaging for longitudinal monitoring of the pathophysiological changes during HCC formation. This work aimed to explore PET-based longitudinal monitoring of oxidative stress metabolism and determine the sensitivity of [18F]-5-fluoroaminosuberic acid ([18F]FASu) for assessing pathophysiological processes in diethylnitrosamine (DEN) induced rat HCC. Methods: Genomic and clinical data were obtained from the HCC dataset (n = 383) in The Cancer Genome Atlas (TCGA-LIHC) and Gene Expression Omnibus (GEO) datasets. Wistar rats were administered DEN weekly, either by gavage (i.g.) at doses of 10 mg/kg or 80 mg/kg or by intraperitoneal injection (i.p.) at 80 mg/kg, with continuous modeling over a 12-week period followed by 24 weeks of consecutive feeding. PET/CT imaging was conducted at weeks 8, 15, and 21 by tail vein injections of [18F]FASu and [18F]FDG (~3.7 MBq). Finally, contrast-enhanced CT imaging of the nodules was performed at the designed time point. The rats in each group were sacrificed at multiple time points to perform a correlation analysis between PET imaging findings and histological examinations. Results: Bioinformatics analysis revealed that upregulation expression of SLC7A11 in HCC indicates oxidative stress-altered cellular metabolism and allows early detection of HCC formation. By simulating different levels of oxidative stress in DEN-induced rat HCC, the SUVmax of [18F]FASu PET imaging positively correlated with the expression of CD44 and SLC7A11 (r = 0.7913, P < 0.0001; r = 0.7173, P < 0.0001, respectively), which maintain redox homeostasis in the cells. Compared with 18F-fluorodeoxyglucose ([18F]FDG), [18F]FASu PET imaging demonstrated higher sensitivity for HCC diagnosis and enabled the characterization of pathological changes in DEN-induced rat HCC at an early stage. Conclusions: Our findings regarding the oxidative stress characterization of HCC formation in DEN-induced rat models using [18F]FASu PET imaging demonstrated the exciting potential of oxidative-stress-related PET imaging for monitoring the pathophysiological changes during HCC formation., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Rationale: Tissue factor (TF) initiates local blood clotting and infiltration of tumor-associated macrophages, leading to tumor recurrence post-local ablation. Our study addressed inefficient cancer cell killing and immunosuppressive macrophage infiltration after percutaneous ethanol injection (PEI) in hepatocellular carcinoma (HCC). We evaluated the feasibility of 18 F-radiolabeled polypeptide TF-targeted radioligand (tTF) as a PET tracer for assessing tumor response. We also explored the efficacy and safety of 177 Lu-radiolabeled tTF to eradicate residual tumors and tumor-associated macrophages. Methods: TF expression in the locally treated human HCC was assessed. Biodistribution, pharmacokinetics, and TF-targeted specificity of Al 18 F-NOTA-tTF were investigated in Kunming (KM) and/or Hepa1-6 mice. Evaluation of FDG/tTF PET imaging, histopathological characteristics, and tumor ablation response was conducted using two incomplete PEI ablation models, with ethanol volumes equivalent to 50% (high-dose (HD) PEI group) or 25% (low-dose (LD) PEI group) of the tumor volume administered. Following PEI, a single dose of 177 Lu-DOTA-tTF was administered on day 1 to assess its efficacy in eradicating residual tumors and immunosuppressive macrophages. Systemic toxicity was evaluated through blood analysis and histological examination of healthy organs. Results: Immunohistochemistry analysis demonstrated elevated TF expression around the ablation margin of residual tissue in human HCC. Radiolabeled tTF exhibited excellent TF-specificity, water solubility, and stability. FDG PET imaging and histological analysis showed tumor recurrence, upregulation of immunosuppressive macrophages, and TF around tumor foci post-treatment in the HD PEI-treated group. Meanwhile, the uptake of 18 F-FDG exhibited a decline, while the uptake of Al 18 F-NOTA-tTF showed an increase in both the HD and LD PEI groups, as observed on day 1 and day 6 post-PEI. These results indicated that increased tTF uptake offers a specific and durable avenue for targeted theranostic applications. Following PEI, 177 Lu-DOTA-tTF therapy demonstrated significant tumor suppression and eradication of immunosuppressive macrophages compared to control groups. Safety assessments indicated no significant toxicity in the main organs of tested animals. Conclusions: Al 18 F-NOTA-tTF is a promising PET tracer for assessing ablated HCC, while 177 Lu-DOTA-tTF provides an effective tool for inhibiting residual tumor growth and immunosuppressive macrophages post-PEI. Significantly, TF-targeting theranostics may help overcome incomplete cancer cell killing and formation of tumor immunosuppressive microenvironment, offering a promising strategy for effective HCC ablation in future clinical practice., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Multiparametric magnetic resonance imaging (mpMRI) is a commonly used method to diagnose pelvic lymph node metastasis (PLNM) in prostate cancer (PCa) patients, but there are few comparative studies on mpMRI and 68 Ga-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) in locally advanced PCa (LAPC) patients. Therefore, we designed a retrospective study to compare the diagnostic value of 68 Ga-PSMA PET/CT and mpMRI for PLNM of LAPC., Methods: A retrospective study was performed on 50 patients with LAPC who underwent radical prostatectomy (RP) in Tongji Hospital from 2021 to 2023. All patients underwent PET/CT and mpMRI examination, and were diagnosed as LAPC before surgery, followed by robot-assisted laparoscopic prostatectomy or laparoscopic RP and extended pelvic lymph node dissection (ePLND). Routine postoperative pathological examination was performed. According to the results, the sensitivity, specificity, positive predictive value, and negative predictive value of 68 Ga-PSMA PET/CT and mpMRI for the diagnosis of PLNM of LAPC were compared., Results: Among the 50 patients, the mean age was 65.5±10.3 years, the preoperative total serum prostate-specific antigen (PSA) was 30.7±12.3 ng/mL, and the Gleason score was 7 [7, 8]. The difference in diagnostic efficacy between 68 Ga-PSMA PET/CT and mpMRI in the preoperative diagnosis of PLNM of PCa was determined by postoperative pathological results. Based on the number of patients who developed PLNM, the sensitivity, specificity, positive predictive value, and negative predictive value of 68 Ga-PSMA PET/CT were as follows: 93.75%, 100.00%, 100.00%, 97.14%, and 68.75%, 97.06%, 91.67%, 86.84% for mpMRI, respectively. Based on the number of pelvic metastatic lymph nodes, the sensitivity, specificity, positive predictive value, and negative predictive value of 68 Ga-PSMA PET/CT were 95.24%, 100.00%, 100.00%, 99.48%, and 65.08%, 99.13%, 89.13%, 96.30% for mpMRI, respectively. It turned out that PET/CT was more sensitive than mpMRI in detecting PLNM of PCa, and the difference was statistically significant., Conclusions: 68 Ga-PSMA PET/CT is more sensitive than mpMRI in the detection of PLNM in patients with LAPC. It is a promising method in the diagnosis and preoperative assessment of PLNM in LAPC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-24-15/coif). The authors have no conflicts of interest to declare., (2024 Translational Andrology and Urology. All rights reserved.)

Perivascular epithelioid cell tumor (PEComa), an uncommon mesenchymal neoplasm, arises from specialized perivascular epithelioid cells exhibiting distinct features of smooth muscle and melanocytic differentiation with unpredictable behavior. PEComa tends to occur more commonly in the uterus and kidneys; its occurrence in the liver is exceedingly rare. We presented a case of a 29-year-old woman with hepatic PEComa and evaluated the tumor with MRI, integrated 18 F-fluorodeoxyglucose (FDG), and 68 Ga-fibroblast activation protein inhibitor (FAPI) PET/CT scans at presentation. The patient had a history of intermittent utilization of oral contraceptive drugs for several years. An abdominal ultrasound in a physical examination from an outside institution revealed a mass in the liver. A contrast-enhanced abdominal MRI revealed restricted diffusion on diffusion-weighted imaging (DWI) and rapid contrast enhancement and washout patterns in the hepatic lesion, suggesting hepatic adenoma (HA) or hepatocellular carcinoma (HCC). Further assessment was carried out using 18 F-FDG and 68 Ga-FAPI PET/CT scans. The hepatic lesion was non-FDG avid, whereas increased tracer uptake was observed on the 68 Ga-FAPI PET/CT. Subsequently, laparoscopic partial resection of liver segment V was performed. Immunohistochemical analyses demonstrated positive staining for HMB45, Melan-A, and SMA while showing negative results for AFP, glypican-3, hepatocyte, and arginase-1. The results were indicative of a hepatic PEComa diagnosis based on these findings. We also review the current literature on the clinical characteristics, pathological features, and challenges in the diagnosis of hepatic PEComa., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhu, Song, Wang, Kuang, Cheng, Zhou and Zou.)

Fibroblast activation protein (FAP) is highly expressed in many tumor types and constitutes a promising target for tumor-specific delivery of therapeutic radionuclides. [ 177 Lu]Lu-DOTAGA.(SA.FAPi) 2 is a novel radiopharmaceutical based on a novel bidentate inhibitor of FAP that is excreted more slowly than its monomeric counterparts. Still, the efficacy of radiotherapy is mitigated by cascades of DNA damage repair signaling in tumor cells including those via Poly(ADP-ribose) polymerase (PARP). We hereby aimed to evaluate the efficacy of [ 177 Lu]Lu-DOTAGA.(SA.FAPi) 2 in combination with a PARP inhibitor, Olaparib, in the 4T1 murine triple negative breast cancer (TNBC) model. The therapeutic efficacy was visualized using 18 F-FDG and [ 68 Ga]Ga-FAPI-04 positron emission imaging/computer tomography (PET/CT). Our results demonstrated that Olaparib suppressed BALB/3T3 fibroblasts in vitro and sensitized the efficacy of [ 177 Lu]Lu-DOTAGA.(SA.FAPi) 2 in mice bearing 4T1 tumors via enhancement of DNA damage. Treatment-associated toxicity was tolerable with only mild leukopenia. Therefore, the combination of [ 177 Lu]Lu-DOTAGA.(SA.FAPi) 2 and Olaparib is a feasible treatment against TNBC.

Abstract: We present image findings of 18F-FDG, 68Ga-FAPI, and 68Ga-DOTATATE PET/CT in a 35-year-old woman with multiple metastases of pancreatic neuroendocrine tumor. The images of PET/CTs using 3 different tracers all showed multiple foci of increased activities in the liver and pancreas body, in which 68Ga-FAPI PET/CT displayed the highest tumor-to-liver ratios. However, 68Ga-DOTATATE PET/CT detected more small metastatic lymph node and bone metastases, which were missed by both FDG and FAPI PET/CT., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Reducing the radiation tracer dose and scanning time during positron emission tomography (PET) imaging can reduce the cost of the tracer, reduce motion artifacts, and increase the efficiency of the scanner. However, the reconstructed images to be noisy. It is very important to reconstruct high-quality images with low-count (LC) data. Therefore, we propose a deep learning method called LCPR-Net, which is used for directly reconstructing full-count (FC) PET images from corresponding LC sinogram data., Methods: Based on the framework of a generative adversarial network (GAN), we enforce a cyclic consistency constraint on the least-squares loss to establish a nonlinear end-to-end mapping process from LC sinograms to FC images. In this process, we merge a convolutional neural network (CNN) and a residual network for feature extraction and image reconstruction. In addition, the domain transform (DT) operation sends a priori information to the cycle-consistent GAN (CycleGAN) network, avoiding the need for a large amount of computational resources to learn this transformation., Results: The main advantages of this method are as follows. First, the network can use LC sinogram data as input to directly reconstruct an FC PET image. The reconstruction speed is faster than that provided by model-based iterative reconstruction. Second, reconstruction based on the CycleGAN framework improves the quality of the reconstructed image., Conclusions: Compared with other state-of-the-art methods, the quantitative and qualitative evaluation results show that the proposed method is accurate and effective for FC PET image reconstruction., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/qims-20-66). Dr. DL serves as an unpaid editorial board member of Quantitative Imaging in Medicine and Surgery. The other authors have no conflicts of interest to declare., (2021 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Accumulating evidence has suggested that the tumor microenvironment of nonsmall-cell lung cancer (NSCLC) may be impacted by chemotherapy, radiotherapy, or epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). PD-L1 is an important biomarker in the tumor microenvironment that can predict patient response to immunotherapies. Therefore, it is highly desirable to achieve a real-time, noninvasive assessment of PD-L1 expression, which can provide critical information for recruiting patients as well as monitoring therapeutic efficacy. We herein studied the EGFR-TKI-induced effects on PD-L1 levels in NSCLC tumor models using immuno-PET imaging with 89 Zr-Df-KN035, an imaging tracer previously established by our group. A549 human NSCLC xenografts were established in BALB/c nude mice and treated with different doses of an EGFR-TKI gefitinib. PET imaging with 89 Zr-Df-KN035 was performed before and after the treatment to evaluate PD-L1 expression, which was further verified by immunohistochemical staining. Our results demonstrate that 89 Zr-Df-KN035 can specifically evaluate PD-L1 levels in NSCLC tumor models. Compared to the untreated control, the high dose of gefitinib inhibited tumor growth and lowered the tumor uptake of 89 Zr-Df-KN035. In comparison, the low dose of gefitinib did not affect tumor growth, although the extensive tumor necrosis also led to the lower uptake of 89 Zr-Df-KN035. In conclusion, our results demonstrate that immuno-PET imaging with 89 Zr-Df-KN035 is a promising tool to noninvasively monitor PD-L1 expression in NSCLC treated with EGFR-TKIs and can be used to optimize treatment plans for immunotherapy.

Multiple hepatic metastases are uncommon as initial presentation of primary anal malignant melanoma. We report FDG PET/CT findings of pathology-proven hepatic metastases from anal malignant melanoma of unknown origin in a 43-year-old woman whose initial presentation was worsening abdominal pain.

Recently, various immuno-PET tracers based on monoclonal antibodies (mAbs), engineered scaffold proteins, and peptides were developed to target either programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1), showing promise in assessment of immune checkpoints. We sought to develop an immunotherapeutic agent based PET probe that enables real-time assessment of PD-L1 expression and evaluation of antibody drug biodistribution to select eligible candidates for anti-PD-1/PD-L1 immunotherapies. KN035, a 79.6 kDa size anti-PD-L1 domain antibody under analysis in clinical trials, was used to develop the immuno-PET probe, 89 Zr-Df-KN035. Immuno-PET studies were performed to monitor PD-L1 levels in nude mice bearing LN229 xenografts with positive expression for PD-L1, and to evaluate the whole-body biodistribution in healthy non-human primates (NHPs). LN229 xenografts were markedly visualized from 24 h after injection of 89 Zr-Df-KN035, with elevated accumulation persisting for up to 120 h. Tumor radioactivity was notably reduced in the presence of excess KN035. Mouse ex vivo biodistribution studies performed at 24 and 120 h revealed tumor-to-muscle ratios as high as 5.64 ± 0.65 and 7.70 ± 1.37, respectively. In the NHP model, PET imaging demonstrated low background. The liver and kidney showed moderate accumulation with the highest SUV mean value of 1.15 ± 0.15 and 2.13 ± 0.10 at 72 h, respectively. The spleen, lymph nodes, and salivary glands were also slightly visualized. In conclusion, 89 Zr-Df-KN035, a novel anti-PD-L1 domain antibody-based probe, shows the feasibility of noninvasive in vivo evaluation of PD-L1 expression. This work further provides a template for immunotherapeutic agent based imaging to evaluate human PD-L1 expression and to augment our understanding of therapeutic agent biodistribution, leading to better therapeutic strategies in the future.

A 47-year-old man presented with abdominal pain, vomiting, and bone pain. Laboratory findings revealed severe hypercalcemia, anemia, and renal insufficiency with decreased serum parathyroid hormone. FDG PET/CT was performed for characteristics suggestive of multiple myeloma and other occult malignancy. The images revealed widespread osteolytic lesions with only 1 focus of definite abnormal FDG uptake. B-cell acute lymphoblastic leukemia was confirmed by pathological examination following bone marrow biopsy.

Glypican-3 (GPC3) is a key member of the glypican family that is expressed on the cell surface by a glycosyl-phosphatidyl-inositol (GPI) anchor. It plays a significant role in hepatocellular carcinoma (HCC) development, angiogenesis, and metastasis. Most HCC overexpress GPC3, whereas little GPC3 can be detected in normal adult liver and benign liver lesions. Therefore, it is important to understand the function of GPC3 in HCC tumor development as the GPC3 ligand may facilitate detection of HCC. In this study, a 12-mer peptide with the sequence of DHLASLWWGTEL (denoted as TJ12P1) was identified by screening a phage display peptide library that demonstrated ideal GPC3 binding affinity. We used TJ12P1 conjugated with near-infrared fluorescent (NIFR) dye Cy5.5 for tumor imaging. After intravenous injection of the imaging agent, TJ12P1, xenografts of high GPC3 expressing hepatocellular carcinoma cell line, HepG2, demonstrated significantly higher tumor accumulation (tumor/muscle ratio: 3.98 ± 0.36) than those of low GPC3 expressing prostate cancer cell line, PC3 (tumor/muscle ratio: 2.03 ± 0.23). More importantly, GPC3 expression in tumor samples of patients could be visualized using TJ12P1, suggesting the potential use of this peptide as a probe for HCC detection. Our study has successfully identified a promising GPC3-binding peptide ligand for detecting the GPC3 expression in HCC not only in vitro but also in vivo by its noninvasive imaging.