- 标题
- 摘要
- 关键词
- 实验方案
- 产品
-
P1217Zirconium-89 labelled probe for molecular imaging of inflammation in experimental atherosclerosis
摘要： Early detection of in?amed atherosclerotic lesions by molecular imaging might improve risk assessment beyond that of vascular stenosis and plaque morphology imaging, and improve the clinical management of high-risk patients. To target the key features of unstable atherosclerotic lesions, we studied the feasibility of our radiotracer, based on modi?ed human serum albumin (HSA), to identify in?amed atherosclerotic lesions by in vivo molecular imaging. We applied a maleylated HSA (Mal-HSA) probe, recognised by scavenger receptors on macrophages, in an experimental imaging study of atherosclerosis. Mal-HSA was coupled with a positron-emitting metal ion, Zirconium-89 (89Zr). The targeting potential of this probe was evaluated and compared with unspeci?c 89Zr-HSA and 18F-FDG in a mouse model of atherosclerosis (Apoe?/?, n=22) and compared with wild-type (WT) mice (C57BL/6, n=21) as controls. Radiotracer accumulation in the aortic arch was analysed in vivo by the fusion of positron emission tomography–magnetic resonance imaging (PET-MRI), radiotracer bio-distribution was measured ex vivo by gamma counter, and plaque uptake was evaluated by phosphor imaging (PI) autoradiography (ARG). PET-MRI, gamma counter measurements, and PI-ARG showed the accumulation of 89Zr-Mal-HSA in the atherosclerotic lesions of Apoe?/? mice. The maximum standardised uptake value (SUVmax) for 89Zr-Mal-HSA at 16 and 20 weeks were 26% and 20% higher (P<0.05) in Apoe?/? mice than control WT mice, whereas no difference in SUVmax was found for 18F-FDG in the same animals. 89Zr-Mal-HSA uptake in the aorta as evaluated by gamma counter 48 h post-injection was 32% higher (P<0.01) for Apoe?/? mice compared to WT mice, and the aorta-to-blood ratio was 10-fold higher (P<0.001) for 89Zr-Mal-HSA compared with unspeci?c 89Zr-HSA. HSA probes were mainly distributed to the liver, spleen, kidneys, bone and lymph nodes. The PI-ARG results corroborated the PET and gamma counter measurements, showing higher accumulation of 89Zr-Mal-HSA in the aortas of Apoe?/? mice compared to WT mice; 9.4±1.4 vs 0.8±0.3% (P<0.001). The modi?ed HSA-based radiotracer showed in vivo targeting of in?amed atherosclerotic lesions of mouse aorta, which could also be veri?ed ex vivo. 89Zr-Mal-HSA seems to be a promising diagnostic tool for the identi?cation of vascular in?ammation. Further methodological studies are needed to verify its applicability for detecting rupture-prone plaques.
关键词： atherosclerosis,inflammation,Zirconium-89,PET-MRI,molecular imaging,Nuclear cardiology
更新于2025-09-23 15:19:57
-
Synthesis and evaluation of zirconium-89 labelled and long-lived GLP-1 receptor agonists for PET imaging
摘要： Introduction: Lately, zirconium-89 has shown great promise as a radionuclide for PET applications of long circulating biomolecules. Here, the design and synthesis of protracted and long-lived GLP-1 receptor agonists conjugated to desferrioxamine and labelled with zirconium-89 is presented with the purpose of studying their in vivo distribution by PET imaging. The labelled conjugates were evaluated and compared to a non-labelled GLP-1 receptor agonist in both in vitro and in vivo assays to certify that the modification did not significantly alter the peptides’ structure or function. Finally, the zirconium-89 labelled peptides were employed in PET imaging, providing visual verification of their in vivo biodistribution. Methods: The evaluation of the radiolabelled peptides and comparison to their non-labelled parent peptide was performed by in vitro assays measuring binding and agonistic potency to the GLP-1 receptor, physicochemical studies aiming at elucidating change in peptide structure upon bioconjugation and labelling as well as an in vivo food in-take study illustrating the compounds’ pharmacodynamic properties. The biodistribution of the labelled GLP-1 analogues was determined by ex vivo biodistribution and in vivo PET imaging. Results: The results indicate that it is surprisingly feasible to design and synthesize a protracted, zirconium-89 labelled GLP-1 receptor agonist without losing in vitro potency or affinity as compared to a non-labelled parent peptide. Physicochemical properties as well as pharmacodynamic properties are also maintained. The biodistribution in rats show high accumulation of radiolabelled peptide in well-perfused organs such as the liver, kidney, heart and lungs. The PET imaging study confirmed the findings from the biodistribution study with a significant high uptake in kidneys and presence of activity in liver, heart and larger blood vessels. Conclusions and Advances in Knowledge: This initial study indicates the potential to monitor the in vivo distribution of long-circulating incretin hormones using zirconium-89 based PET.
关键词： GLP-1,Bioconjugation,PET,Molecular imaging,Zirconium-89,Radiolabelling
更新于2025-09-12 10:27:22
-
Zirconium-89 chloride can be used for immuno-PET radiochemistry without loss of antigen reactivity in vivo
摘要： Zirconium-89 (89Zr) immuno-PET continues to be assessed in numerous clinical trials. This report evaluates the use of zirconium-89 chloride (89Zr-ZrCl4) in the radiolabelling of monoclonal antibodies (mAbs) conjugated with desferrioxamine B (DFO), describes its effects on radiopharmaceutical reactivity toward antigen and offers guidance on how to ensure long-term stability and purity. Methods: 89Zr-Zr-DFO-trastuzumab and 89Zr-Zr-DFO-cetuximab were prepared using 89Zr-ZrCl4. The stability of each was evaluated for 7 days in 20 mM histidine/240 mM sucrose buffer, 0.25 M sodium acetate (NaOAc) buffer containing 5 mg?mL-1 n-acetyl-L-cysteine (NAC) or 0.25 M NaOAc containing 5 mg?mL-1 L-methionine (L-MET). To assess antigen reactivity, 89Zr-Zr-DFO-trastuzumab was evaluated using the Lindmo method and tested in PET/CT imaging of mouse models of human epidermal growth factor receptor 2 (HER2+/-) lung cancer. Results: Using 89Zr-ZrCl4, 89Zr-Zr-DFO-trastuzumab and 89Zr-Zr-DFO-cetuximab were prepared with increased specific activity and retained purities of 95% after 3 days when formulated in sodium acetate buffer containing L-MET. Based upon Lindmo analysis and small animal PET/CT imaging, 89Zr-Zr-DFO-trastuzumab remained reactive toward antigen after being prepared with 89Zr-ZrCl4. Conclusion: 89Zr-ZrCl4 facilitated the radiosynthesis of 89Zr-immuno-PET agents with increased specific activity. L-MET enhanced long-term solution stability better than all other formulations examined, and 89Zr-Zr- DFO-trastuzumab remained reactive toward antigen. While further evaluation is necessary, these initial results suggest that 89Zr-ZrCl4 may be useful in immuno-PET radiochemistry as radiolabeled mAbs are increasingly integrated into precision medicine strategies.
关键词： zirconium-89 chloride,immuno-PET,stability
更新于2025-09-10 09:29:36