microPET

Joint injury is associated with risk for development of osteoarthritis (OA). Increasing evidence suggests that activation of fibrinolysis is involved in OA pathogenesis. However, the role of the fibrinolytic pathway is not well understood. Here we showed that the fibrinolytic pathway, which includes plasminogen/plasmin, tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA) and the uPA receptor (uPAR), were dysregulated in human OA joints. Pharmacological inhibition of plasmin attenuated OA progression in a destabilization of the medial meniscus (DMM) mouse model, while genetic deficiency of plasmin activator inhibitor (PAI-1), or injection of plasmin, exacerbated OA...

BACKGROUND/AIM: Since the use of anaesthetics has the drawback of altering radiotracer distribution, preclinical positron emission tomography (PET) imaging findings of anaesthetised animals must be carefully handled. This study aimed at assessing the cerebral [18 F]F-FDG uptake pattern in healthy Wistar rats under four different anaesthesia protocols using microPET/magnetic resonance imaging (MRI) examinations. MATERIALS AND METHODS: Post-injection of 15±1...

PURPOSE: Vascular endothelial growth factor receptor 3 (VEGFR-3) plays a critical role in tumor lymphangiogenesis and metastasis, holding promise as a promising therapeutic target for solid tumors. TMVP1 (LARGR) is a 5-amino acid peptide previously identified in our laboratory from bacterial peptide display system that specifically targets VEGFR-3. Radiolabeled TMVP1 can be used for non-invasive imaging of VEGFR-3 expressing tumors. Homodimeric peptides have better targeting ability than monomeric peptides, and it is worth exploring whether homodimers of TMVP1 ((TMVP1)2 ) can achieve better imaging effects...

UNLABELLED: Integrin receptor αv β3 and gastrin-releasing peptide receptor (GRPR) expression of tumors could be detected using PET imaging with radiolabeled Arg-Gly-Asp (RGD) and the antagonistic bombesin analog RM26, respectively. The purpose of this study was to investigate the dual receptor-targeting property of the heterodimer RGD-RM26-03 (denoted as LNC1015), demonstrate the tumor diagnostic value of [68 Ga]Ga-LNC1015 in preclinical experiments, and evaluate its preliminary clinical feasibility...

Cathepsin B, a lysosomal protease, is considered as a crucial biomarker for tumor diagnosis and treatment as it is overexpressed in numerous cancers. A stimulus-responsive SF scaffold has been reported to detect the activity of a variety of tumor-associated enzymes. In this work, a small-molecule PET tracer ( [ 68 Ga]NOTA-SF-CV ) was developed by combining an SF scaffold with a cathepsin B-specific recognition substrate Cit-Val. Upon activation by cathepsin B, [ 68 Ga]NOTA-SF-CV could form the cyclization product in a reduction environment, resulting in reduced hydrophilicity...

BACKGROUND: Brain ischemia-reperfusion injury is a complex process, and neuroinflammation is an important secondary contributing pathological event. Neutrophils play major roles in ischemic neuroinflammation. Once activated, neutrophils express formyl peptide receptors (FPRs), which are special receptors of a class of chemoattractants and may be potential targets to regulate the activity of neutrophils and control cerebral ischemic injury. This study was aimed to explore the ameliorating effect of Cyclosporin H (CsH), a potent FPR antagonist, on brain ischemic injury by inhibiting the activation and migration of neutrophils, and improving cerebral blood flow...

There is evidence that maternal milieu and changes in environmental factors during the prenatal period may exert a lasting impact on the brain health of the newborn, even in case of neonatal brain hypoxia-ischemia (HI). The present study aimed to investigate the effects of maternal environmental enrichment (EE) on HI-induced energetic and metabolic failure, along with subsequent neural cell responses in the early postnatal period. Male Wistar pups born to dams exposed to maternal EE or standard conditions (SC) were randomly divided into Sham-SC, HI-SC, Sham-EE, and HI-EE groups...

Human bacterial infections significantly contribute to the increase in healthcare-related burdens. This scenario drives the study of novel techniques for the early and precise diagnosis of infectious processes. Some alternatives include Nuclear Medicine- and Molecular Imaging-based strategies. However, radiopharmaceuticals that are available for routine assessments are not specific to differentiating infectious from aseptic inflammatory processes. In this context, [68 Ga]Ga-DOTA-Ubiquicidin29-41 was synthesized using an automated module and radiochemical; in vivo and in vitro studies were performed...

UNLABELLED: Due to the heterogeneity of tumors, strategies to improve the effectiveness of dual-targeting tracers in tumor diagnostics have been intensively practiced. In this study, the radiolabeled [18 F]AlF-NOTA-FAPI-RGD (denoted as [18 F]AlF-LNC1007), a dual-targeting heterodimer tracer targeting both fibroblast activation protein (FAP) and integrin αv β3 to enhance specific tumor uptake and retention, was synthesized and evaluated. The tracer was compared with [68 Ga]Ga-LNC1007 in preclinical and clinical settings...

PURPOSE: Enzymolysis clearance strategy, characterized by releasing the non-reabsorbable radioactive fragment under the specific cleavage of enzymes, is confirmed to be a safe and effective way to reduce the renal radioactivity accumulation in mice. However, the effectiveness of this strategy in humans remains unknown. Human epidermal growth factor receptor 2 (HER2) is overexpressed in various types of tumors, and radiolabeled HER2 Affibody is believed to be an attractive tool for HER2-targeted theranostics...

INTRODUCTION: Functions of existing automatic module systems for synthesis of radiopharmaceuticals mainly focus on the radiolabeling of small molecules. There are few modules which have achieved full-automatic radiolabeling of non-metallic and metallic nuclides on small molecules, peptides, and antibody drugs. This study aimed to develop and test a full-automatic multifunctional module system for the safe, stable, and efficient production of radiopharmaceuticals. METHODS: According to characteristics of labeling process of radioactive drugs, using UG and Solidworks softwares, full-automatic cassette-based synthesis module system Mortenon M1 for synthesis of radiopharmaceuticals with various radionuclides, was designed and tested...

Anthracyclines' cardiotoxicity involves an accelerated generation of reactive oxygen species. This oxidative damage has been found to accelerate the expression of hexose-6P-dehydrogenase (H6PD), that channels glucose-6-phosphate (G6P) through the pentose phosphate pathway (PPP) confined within the endoplasmic/sarcoplasmic reticulum (SR). To verify the role of SR-PPP in the defense mechanisms activated by doxorubicin (DXR) in cardiomyocytes, we tested the effect of this drug in H6PD knockout mice (H6PD-/- )...

Purpose Combined micro-PET/CT scanners are widely employed to investigate models of brain disorders in rodents using PET-based coregistration. We examined if CT-based coregistration could improve estimates of brain dimensions and consequently estimates of nondisplaceable binding potential (BP ND ) in rodent PET studies. Procedures PET and CT scans were acquired on 5 female and 5 male CD-1 mice with PET and CT scans were acquired on 5 female and 5 male CD-1 mice with 3-[ 18 F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([ 18 F]FPEB), a radiotracer for the metabotropic glutamate receptor subtype 5 (mGluR5)...

UNLABELLED: The mesenchymal epithelial transition factor (c-Met) is frequently overexpressed in numerous cancers and has served as a validated anticancer target. Inter- and intra-tumor heterogeneity of c-Met, however, challenges the use of anti-MET therapies, highlighting an urgent need to develop an alternative tool for visualizing whole-body c-Met expression quantitatively and noninvasively. Here we firstly reported an 18 F labeled, small-molecule quinine compound-based PET probe, 1-(4-(5-amino-7-(trifluoromethyl) quinolin-3-yl) piperazin-1-yl)-2-(fluoro-[18F]) propan-1-one, herein referred as [18F]-AZC...

To better diagnose and treat tumors related to arginine metabolism, (2S,4S)-2-amino-4-(4-(2-(fluoro-18 F)ethoxy)benzyl)-5-guanidinopentanoic acid ( [18 F]7 ) was designed and prepared by introducing [18 F]fluoroethoxy benzyl on carbon-4 of arginine. [18 F]7 and 7 were successfully prepared using synthesis methods similar to those used for (2S,4S)-4-[18 F]FEBGln and (2S,4S)-4-FEBGln, respectively. In vitro experiments on cell transport mechanisms showed that [18 F]7 was similar to (2S,4S)4-[18 F]FPArg and was transported into tumor cells by cationic amino acid transporters...

18 F-fluorodeoxyglucose positron emission tomography (18 F-FDG PET) has been widely utilized for tumor diagnosis. Hyperglycemia affects the 18 F-FDG uptake and reduces tumor-to-tissue contrasts, however, ideal hypoglycemic drugs are lacking. This study compared the role of insulin with the novel widely used hypoglycemic drug, sodium-glucose cotransporter 2 (SGLT2) inhibitor, on 18 F-FDG PET imaging in diabetic conditions. The streptozotocin (STZ)-induced diabetic C57BL/6N mice were inoculated with B16 (mouse melanoma) cells to establish the xenograft tumor model...

Malignant melanoma has an aggressive nature and a high metastatic propensity resulting in the highest mortality rate of any skin cancer. In this study, we synthesized 18 F-labeled procainamide (PCA) for detection of melanoma using positron emission tomography (PET), and evaluated its biological characteristics. The non-decay-corrected radiochemical yield of 18 F-PCA was 10-15% and its in vitro stability was over 98% for 2 hours. At 1 hour, cellular uptake of 18 F-PCA was 3.8-fold higher in a group with the presence of L-tyrosine than in a non-L-tyrosine-treated group...

Fibroblast activation protein (FAP) is a promising molecular target for imaging in various types of cancers. Several 18 F-labeled FAP inhibitor (FAPI) tracers have been evaluated in clinical study. However, these tracers display high physiological uptake in gallbladder and bile duct system. To overcome the limitation, we herein designed a novel radiotracer named 18 F-FAPTG. 18 F-FAPTG was produced with a non-decay-corrected radiochemical yield of 24.0 ± 6.0% and 22.0 ± 7.0% for manual and automatic synthesis, respectively...

Although radiolabeled alpha-melanocyte stimulating hormone-analogue NAPamide derivatives are valuable melanoma-specific diagnostic probes, their rapid elimination kinetics and high renal uptake may preclude them from being used in clinical settings. We aimed at improving the pharmacokinetics of radiolabeled DOTA-NAPamide compounds by incorporating a 4-(p-iodo-phenyl)-butanoic acid (IPB) into the molecules. Followed by 68 Ga-, 205/206 Bi-, and 177 Lu-labelling, the radiopharmaceuticals ([68 Ga]Ga-DOTA-IPB-NAPamide, [205/206 Bi]Bi-DOTA-IPB-NAPamide, [177 Lu]Lu-DOTA-IPB-NAPamide) were characterized in vitro...

Background: NOX4 is highly expressed in breast cancer and is closely associated with cell invasion and metastasis. The involvement of NOX4 in glycolysis in breast cancer remains unclear. The aim of this study was to investigate the role and mechanism of NOX4 in glycolysis in breast cancer. Methods: NOX4 expression in breast cancer cells was detected by qRT-PCR and western blotting. siRNAs and plasmids were used to silence or enhance the expression of NOX4. The mRNA and protein expression of HK2, GLUT1, PKM2, LDHA, and YAP was detected by qRT-PCR and western blotting, and the 18 F-FDG uptake rate was detected by γ-radiometer...