Radioactive and Fluorescent Dual Modality Cysteine Cathepsin B Activity-Based Probe for Cancer Theranostics.

Cysteine cathepsin B (CTS-B) is a crucial enzyme that is overexpressed in numerous malignancies and contributes to the invasion and metastasis of cancer. Therefore, this study sets out to develop and evaluate an activity-based multimodality theranostic agent targeting CTS-B for cancer imaging and therapy. A CTS-B activity-based probe, BMX2, was synthesized and labeled efficiently with 68Ga and 90Y to produce 68Ga-BMX2 for multimodality imaging and 90Y-BMX2 for radiation therapy. The affinity and specificity of BMX2 binding with the CTS-B enzyme were determined by fluorescent western blots using recombined active human CTS-B enzyme (rh-CTS-B) and four cancer cell lines including HeLa, HepG2, MCF7, and U87MG, with CA074 as the CTS-B inhibitor for control. Confocal laser scanning microscope imaging and cell uptake measurement were also performed. Then, in vivo PET imaging and fluorescence imaging were acquired on HeLa xenografts. Finally, the therapeutic effect of 90Y-BMX2 was tested. BMX2 could be specifically activated by rh-CTS-B and stably bound to the enzyme. The binding of BMX2 with CTS-B is time-dependent and enzyme concentration-dependent. Although CTS-B expression varied between cell lines, all showed significant uptake of BMX2 and 68Ga-BMX2. In vivo optical and PET imaging showed a high tumor uptake of BMX2 and 68Ga-BMX2 and accumulation for more than 24 h. 90Y-BMX2 could significantly inhibit HeLa tumor growth. The development of 68Ga/90Y-BMX2, a radioactive and fluorescent dual modality theranostic agent, demonstrated an effective theranostic approach for PET diagnostic imaging, fluorescence imaging, and radionuclide therapy of cancers, which may have a potential for clinical translation for cancer theranostics in the future.

[18F-FDG PET/CT features on paraganglioma of testis with multiple lymph node and lung metastasis: A case report and literature review].

OBJECTIVE: To determine the clinicopathological and imaging features in 18F-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography and computed tomography (PET/CT) for paraganglioma of testis, and to increase the diagnostic accuracy.
 Methods: A case of paraganglioma of testis with multiple lymph node and lung metastasis were reported. PET/CT and pathological findings in the case were retrospectively analyzed.
 Results: The patient presented with high blood pressure, high level of catecholamine, and urinary vanillylmandelic acid. The patient underwent 18F-FDG PET/CT, which showed the features including the right testis nodule with a star lesion nearby, the right spermatic cord, the lymphadenopathy of bilateral inguinal and retroperitoneum, the posterior basal segment of right lung nodule, and a lot of brown adipose tissues (BAT) in the whole body with intense FDG uptake. 18F-FDG PET/CT showed that the intense FDG uptake of the BAT disappeared after the excision of the right testis and metastasis of paraganglioma.
 Conclusion: PET/CT shows great value in localization diagnose, clinical staging and curative evaluation. PET/CT plays a helpful role in revealing the BAT with 18F-DG avidity in the patients with paraganglioma with elevated blood pressure, high level catecholamine, and urinary vanillylmandelic acid.

Novel PET Imaging Probe for Quantitative Detection of Senescence In Vivo.

Real-time detection of cellular senescence remains a clinical challenge. Here, we aimed to develop a positron emission tomography (PET) imaging probe targeting senescence-associated ß-galactosidase (SA-ß-Gal), the most widely used biomarker of cellular senescence, and investigate its performance for real-time in vivo quantitative detection of cellular senescence. A stable PET imaging agent [68Ga]Ga-BGal was obtained with a high labeling yield (90.0 ± 4.3%) and a radiochemical purity (>95%). [68Ga]Ga-BGal displayed high sensitivity and specificity for ß-Gal both in vitro and in vivo. The reaction and uptake of the probe correlated with the ß-Gal concentration and reaction time. In PET imaging, high ß-Gal-expressing CT26.CL25 tumors and doxorubicin-treated HeLa tumors showed high signals from [68Ga]Ga-BGal, while a low signal was observed in CT26.WT and untreated HeLa tumors. In summary, we showcased successful PET imaging of senescence in preclinical models using probe [68Ga]Ga-BGal. This finding holds the potential for translating senescence imaging into clinical applications.

FOXO3-Activated circFGFBP1 Inhibits Extracellular Matrix Degradation and Nucleus Pulposus Cell Death via miR-9-5p/BMP2 Axis in Intervertebral Disc Degeneration In Vivo and In Vitro.

(1) Background: intervertebral disc degeneration (IVDD) defined as the degenerative changes in intervertebral disc is characterized by extracellular matrix (ECM) degradation and death in nucleus pulposus (NP) cells. (2) Methods: The model of IVDD was established in male Sprague Dawley rats using a puncture of a 21-gauge needle at the endplates located in the L4/5 intervertebral disc. Primary NP cells were stimulated by 10 ng/mL IL-1ß for 24 h to mimic IVDD impairment in vitro. (3) Results: circFGFBP1 was downregulated in the IVDD samples. circFGFBP1 upregulation inhibited apoptosis and extracellular matrix (ECM) degradation and promoted proliferation in IL-1ß-stimulated NP cells. Additionally, circFGFBP1 upregulation mitigated the loss of NP tissue and the destruction of the intervertebral disc structure in vivo during IVDD. FOXO3 could bind to the circFGFBP1 promoter to enhance its expression. circFGFBP1 upregulated BMP2 expression in NP via sponging miR-9-5p. FOXO3 enhanced the protection of circFGFBP1 in IL-1ß-stimulated NP cells, whereas a miR-9-5p increase partly reversed the protection. miR-9-5p downregulation contributed to the survival of IL-1ß-stimulated NP cells, which was partially reversed by BMP2 silence. (4) Conclusions: FOXO3 could activate the transcription of circFGFBP1 via binding to its promoter, which resulted in the enhancement of BMP2 via sponging miR-9-5p and then inhibited apoptosis and ECM degradation in NP cells during IVDD.

18F-FDG PET/CT Associates With Disease Activity and Clinical Recurrence of AOSD Patients.

Objective: The purpose of this study was to explore the value of 18F-FDG PET/CT in monitoring the disease activity and predicting the prognosis of the Adult-onset Still's disease (AOSD). Methods: We retrospectively analyzed the electronic medical records of 45 AOSD patients who underwent 18F-FDG PET/CT in the Second Xiangya Hospital. PET/CT imaging and clinical information were retrospectively reviewed and analyzed. 18F-FDG uptake was assessed by measuring standard uptake value (SUV) in the spleen, liver, bone marrow, and lymph nodes. The spleen-to-liver ratio of the SUVmax (SLRmax) and SUVmean (SLRmean), the bone-to-liver ratio of the SUVmax (BLRmax), and SUVmean (BLRmean), and the lymph nodes-to-liver ratio of the SUVmax (LyLRmax) were calculated. Clinical and laboratory information were collected and evaluated for association with metabolic parameters of 18F-FDG PET/CT. The influencing factors for recurrence within 1 year were analyzed to determine whether 18F-FDG PET/CT can predict the prognosis of AOSD patients. Results: Elevated 18F-FDG uptake could be observed in bone marrow, spleen, and lymph nodes of AOSD patients. Correlation analysis between 18F-FDG uptake of organs and laboratory examinations showed that SLRmean positively correlated with LDH, AST, ferritin, and the systemic score (r = 0.572, 0.353, 0.586, and 0.424, P < 0.05). The SLRmean had the highest correlation with ferritin (r = 0586, P < 0.001). All metabolic parameters in spleen, including SUVmax, SUVmean, SLRmax, and SLRmean, are positively correlated with LDH level (r = 0.405, 0.539, 0.481, and 0.572, P < 0.05). Bone marrow SUVmax, BLRmax, and BLRmean were correlated with C-reactive protein (CRP) level (r = 0.395, 0.437, and 0.469, P < 0.05). Analysis of the influencing factors of recurrence within 1 year showed that the spleen SUVmax, spleen SUVmean, SLRmax, SLRmean, ferritin, and the systemic score of the recurrence group was significantly higher than the non-recurrence group (P < 0.05). The SLRmean cutoff of 1.66 with a sensitivity of 72.7% and specificity of 80.0% had the highest performance in predicting recurrence. Conclusion: The glucose metabolism of the liver, spleen, and bone marrow of AOSD patients were correlated with laboratory inflammatory indicators and system score, suggesting that 18F-FDG PET/CT could be applied to evaluate disease activity. Moreover, spleen 18F-FDG uptake may be a potential biomarker for predicting clinical prognosis of AOSD patients.

Primary splenic epithelioid hemangioendothelioma with diffuse metastases revealed by FDG PET/CT imaging: A case report.

RATIONALE: Epithelioid hemangioendothelioma (EHE) is a rare low-to-intermediate grade malignant vascular neoplasm. We report a primary splenic EHE with diffused metastasis who underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). Our case emphasizes that EHE should be considered a differential diagnose of 18F-FDG-avid splenic malignancies. PATIENT CONCERNS: A 39-year-old man presented with abdominal distension and chest distress for 20 days and lumbago for 2 days. Transthoracic echocardiography suggested a large amount of pericardial effusion. Contrast-enhanced CT imaging showed splenomegaly with multiple low-density nodules with ring enhancement. A large irregular mass was also found in the right superior mediastinum with heterogeneous density and enhancement. 18F-FDG PET/CT imaging revealed splenomegaly, filled with intense hypermetabolic nodules and masses. And multiple regions of increased 18F-FDG uptake were observed in the mediastinum, left pleura, and bones. DIAGNOSIS: EHE of the spleen. INTERVENTIONS: Half a month after the diagnosis was confirmed, the patient then underwent chemotherapy, Docetaxel combined with carboplatin, and Endu were administrated every 3 weeks. OUTCOMES: During the 6-month follow-up period, the patient has finished 4 cycles of chemotherapy combined with 2 months of targeted drug. Efficacy assessment is partial remission through CT imaging, and clinical symptoms of patient improved significantly. LESSONS: Primary splenic EHE is extremely rare, especially with diffuse systemic metastasis. Our report suggested that EHE should be considered a differential diagnosis of 18F-FDG-avid splenic malignancies. Furthermore, 18F-FDG PET/CT plays critical role in staging and accessing disease extent of EHE.

Kinetic magnetic resonance imaging analysis of thoracolumbar segmental mobility in patients without significant spondylosis.

To observe thoracolumbar segmental mobility using kinetic magnetic resonance imaging (kMRI) in patients with minimal thoracolumbar spondylosis and establish normal values for translational and angular segmental motion as well as the relative contribution of each segment to total thoracolumbar segmental motion in order to obtain a more complete understanding of this segmental motion in healthy and pathological conditions.Mid-sagittal images obtained by weight-bearing, multi-position kMRI in patients with symptomatic low back pain or radiculopathy were reviewed. The translational motion and angular variation of each segment from T10-L2 were calculated using MRAnalyzer Automated software. Only patients with a Pfirrmann grade of I or II, indicating minimal disc disease, for all thoracolumbar discs from T10-T11 to L1-L2 were included for further analysis.The mean translational motion measurements for each level of the lumbar spine were 1.15 mm at T10-T11, 1.20 mm at T11-T12, 1.23 mm at T12-L1, and 1.34 mm at L1-L2 (P < .05 for L1-L2 vs T10-T11). The mean angular motion measurements at each level were 3.26° at T10-T11, 3.92° at T11-T12, 4.95° at T12-L1, and 6.85° at L1-L2. The L1-L2 segment had significantly more angular motion than all other levels (P < .05). The mean percentage contribution of each level to the total angular mobility of the thoracolumbar spine was highest at L1-L2 (36.1%) and least at T10-T11 (17.1%; P < .01).Segmental motion was greatest in the proximal lumbar levels, and angular motion showed a gradually increasing trend from T10 to L2.

Diffuse hepatic epithelioid hemangioendothelioma with multiple splenic metastasis and delayed multifocal bone metastasis after liver transplantation on FDG PET/CT images: A case report.

RATIONALE: Malignant hepatic epithelioid hemangioendotheliom (HEH) is a rare vascular tumor of endothelial origin, with multiple metastases to the spleen. This report describes a diffuse HEH with splenic metastasis on 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) images and delayed mutifocal bone metastasis after liver transplantation (LTx). PATIENT CONCERNS: A 30-year-old male was admitted to our hospital with a complaint of abdominal distension, fatigue, and anorexia for 2 months. DIAGNOSES: Mild to moderate FDG uptake in the whole liver, and multifocal FDG uptake in the spleen were observed on 18F-FDG PET/CT scan. Ultrasound guided liver biopsy was performed, and a diagnosis of HEH was confirmed. INTERVENTIONS: The patient underwent LTx and splenectomy. OUTCOMES: The patient developed low back pain due to unknown etiology, 3 months after surgery. A follow-up 18F-FDG PET/CT scan demonstrated multifocal bone destruction. Unfortunately, the patient died 12 months after surgery. LESSONS: It is noteworthy that despite liver transplantation for the treatment of HEH, there may be a risk of recurrence. For these patients with extrahepatic lesions, adjuvant chemotherapy may be a useful alternative treatment method for the prevention of recurrence.