Synthesis, in vitro evaluation, and68Ga-radiolabeling of CDP1 toward PET/CT imaging of bacterial infection

Gold nanoclusters (AuNCs) have gained popular attention in recent years because of their efficient tumor accumulation through EPR effect and renal clearance. In this work, we put forward a new approach to prepare glutathione-coated, 68Ga-labeled AuNCs (68Ga-GHS@AuNCs) with ultrasmall sizes (< 2 nm) for PET/CT imaging of tumors. GHS@AuNCs has low cytotoxicity in vitro. PET/CT imaging revealed that the 68Ga-GHS@AuNCs could target tumor and be cleared by kidney efficiently. Our study demonstrates that 68Ga-GHS@AuNCs has great potential for detection of tumors.

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Abstract 5788: VCAM-1 Targeted PET-CT Detects Inflammatory Atherosclerotic Plaques

Circulation ◽

10.1161/circ.118.suppl_18.s_102-a ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Matthias Nahrendorf ◽

Edmund Keliher ◽

Peter Panizzi ◽

Hanwen Zhang ◽

Sheena Hembrador ◽

...

Keyword(s):

Dynamic Range ◽

Atherosclerotic Lesion ◽

Vascular Anatomy ◽

High Sensitivity ◽

Ct Imaging ◽

Atherosclerotic Plaques ◽

Mrna Levels ◽

Pet Ct

Hybrid PET-CT imaging of VCAM-1 expression and vascular anatomy may facilitate simultaneous assessment of atherosclerotic lesion biology and morphology, and enhance risk assessment in individual patients. We used combined in vitro/in vivo screening of candidate affinity ligands and developed a PET reporter for imaging VCAM-1 expression with high sensitivity, specificity and translational potential. Three different phage display-derived VCAM-1 affinity peptides were tested using immobilized VCAM-1, VCAM-1 expressing cells and apoE−/− mice. A compound with a linear peptide and arborising tetrameric design showed high affinity (86.6 nM) and specificity for VCAM-1 (97% inhibition with soluble VCAM-1). This lead compound was derivatized with 18Fluorine to synthesize the clinically viable PET agent 18F-4V. In vivo PET-CT imaging showed robust uptake of 18F-4V in plaque laden arterial sections from 8 apoE−/− mice, significantly higher than in 4 wild type mice and attenuated by atorvastatin treatment (p<0.05). 18F-4V uptake was confirmed in excised aortas, colocalized with atherosclerotic plaques delineated by Oil Red O staining and correlated with mRNA levels of VCAM-1 measured by quantitative RT-PCR (R2=0.62, p=0.03). 18F-4V allows noninvasive PET-CT imaging of VCAM-1 in atheromata, has sufficient dynamic range to quantify treatment effects, and correlates with inflammatory gene expression. This approach lends itself to seamless translation to human PET-CT imaging.

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[18F]Nifene PET/CT Imaging in Mice: Improved Methods and Preliminary Studies of α4β2* Nicotinic Acetylcholinergic Receptors in Transgenic A53T Mouse Model of α-Synucleinopathy and Post-Mortem Human Parkinson’s Disease

Molecules ◽

10.3390/molecules26237360 ◽

2021 ◽

Vol 26 (23) ◽

pp. 7360

Author(s):

Anthony-David T. Campoy ◽

Christopher Liang ◽

Reisha M. Ladwa ◽

Krystal K. Patel ◽

Ishani H. Patel ◽

...

Keyword(s):

Parkinson’S Disease ◽

Mouse Model ◽

Pet Imaging ◽

Ct Imaging ◽

Anterior Cingulate ◽

Pet Ct ◽

Mice Brain ◽

Improved Methods

We report [18F]nifene binding to α4β2* nicotinic acetylcholinergic receptors (nAChRs) in Parkinson’s disease (PD). The study used transgenic Hualpha-Syn(A53T) PD mouse model of α-synucleinopathy for PET/CT studies in vivo and autoradiography in vitro. Additionally, postmortem human PD brain sections comprising of anterior cingulate were used in vitro to assess translation to human studies. Because the small size of mice brain poses challenges for PET imaging, improved methods for radiosynthesis of [18F]nifene and simplified PET/CT procedures in mice were developed by comparing intravenous (IV) and intraperitoneal (IP) administered [18F]nifene. An optimal PET/CT imaging time of 30–60 min post injection of [18F]nifene was established to provide thalamus to cerebellum ratio of 2.5 (with IV) and 2 (with IP). Transgenic Hualpha-Syn(A53T) mice brain slices exhibited 20–35% decrease while in vivo a 20–30% decrease of [18F]nifene was observed. Lewy bodies and α-synuclein aggregates were confirmed in human PD brain sections which lowered the [18F]nifene binding by more than 50% in anterior cingulate. Thus [18F]nifene offers a valuable tool for PET imaging studies of PD.

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Preclinical and Exploratory Clinical Studies of Novel 68Ga-labeled ᴅ-Peptide Antagonist for PET Imaging of TIGIT Expression in Cancers

10.21203/rs.3.rs-1022828/v1 ◽

2021 ◽

Author(s):

Xiaobo Wang ◽

Ming Zhou ◽

Bei Chen ◽

Huanhuan Liu ◽

Jianyang Fang ◽

...

Keyword(s):

Pilot Study ◽

Pet Imaging ◽

Ex Vivo ◽

Ct Imaging ◽

Whole Body ◽

Binding Assays ◽

Pet Ct ◽

Peptide Antagonist

Abstract Purpose While TIGIT has been propelled under the spotlight as a next-generation target in cancer immunotherapy, anti-TIGIT therapy seems to be promising for a fraction of patients in clinical trials. Therefore, patient stratification is critical for this therapy, which could benefit from a whole-body, non-invasive and quantitative evaluation of TIGIT expression in cancers. In this study, a 68Ga-labeled ᴅ-peptide antagonist, 68Ga-GP12, was developed and validated for PET imaging of TIGIT expression in vitro, in vivo, and first-in-human pilot study. Methods The ᴅ-enantiomer peptide antagonists were modified and radiolabeled with 68Ga. In vitro binding assays were performed in human peripheral blood mononuclear cells (PBMCs) to assess their affinity and specificity. The imaging capacity, biodistribution, pharmacokinetics, and radiation dosimetry were investigated in vivo. Flow cytometry, autoradiography, and immunohistochemical staining were used to confirm the expression of TIGIT ex vivo. The safety and potential of 68Ga-GP12 for PET/CT imaging of TIGIT expression were further evaluated in a first-in-human pilot study with advanced NSCLC. Results 68Ga-labeled ᴅ-peptides were conveniently produced with high radiochemical yields,radiochemical purity and molar activities. In vitro binding assays demonstrated 68Ga-GP12 has favorable affinity and specificity for TIGIT with a KD of 37.28 nM. In vivo and ex vivo studies demonstrated the favorable pharmacokinetics of 68Ga-GP12 for PET imaging of TIGIT expression with high tumor uptake of 4.22 ± 0.68 %ID/g and the tumor-to-muscle ratio of 12.94 ± 2.64 at 60 min post-injection. The primary and metastatic lesions found in the first-in-human studies of 68Ga-GP12 PET/CT imaging were comparable to that in 18F-FDG PET/CT imaging. Moreover, the inhomogenous intra-and-inter-tumoral uptake of 68Ga-GP12 was presented, reflecting the heterogeneity of TIGIT expression levels. Conclusion 68Ga-GP12 is a promising radiotracer for PET imaging of TIGIT expression in cancers, indicating its potential as a potential companion diagnostic for anti-TIGIT therapies.

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