Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

Objectives:To establish a candidate reference measurement procedure based on isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) for cyclosporin A, tacrolimus, sirolimus, and everolimus measurements in human whole blood.Methods:The isotope labeled cyclosporine A, tacrolimus, sirolimus, and everolimus were selected as the internal standards. Samples were accurately weighed while protein precipitation and solid phase extraction were selected for the sample preparation. The standard curve method was applied for quantification. The ultra-high liquid chromatography coupled with triple quadrupole mass spectrometer was used for analysis. The specificity, matrix effect, detection limit, quantification limit, precision, accuracy, and uncertainty of the method were evaluated.Results:The method showed good selectivity and specificity. No apparent interferences or matrix effects were found in the target analyte measurements. The detection limits and quantification limits of cyclosporin A, tacrolimus, sirolimus and everolimus met clinical requirements. Intra-batch coefficients of variation ( CV) were from 1.4% to 1.8% for CSA, from 1.7% to 2.8% for TAC, from 1.3% to 3.7% for SRL and from 2.3% to 3.2% for EVR, and total CVs were from 1.8% to 2.9% for CSA, from 1.7% to 3.8% for TAC, from 2.6% to 4.7% for SRL and from 3.5% to 4.6% for EVR. The relative recoveries were from 97.9% to 100.3% for CSA, from 98.4% to 103.1% for TAC, from 99.4% to 102.0% for SRL and from 98.3% to 99.4% for EVR, and the relative expanded uncertainties at four concentrations were from 4.2% to 4.4% for CSA, from 1.5% to 2.4% for TAC, from 4.4% to 4.9% for SRL and from 2.2% to 2.7% for EVR. Conclusion:A candidate reference measurement procedure for the cyclosporine A, tacrolimus, sirolimus, and everolimus in human whole blood was established by ID-LC-MS/MS.

Objective:To review the imaging characteristics and evaluate the diagnostic value of Doppler echocardiography for congenitally malposition of septum primum(MSP).Methods:Images of Doppler echocardiography were retrospectirely rewiewed and compared with CTA, operative and necropsy findings in 8 cases with MSP in Xinhua Hospital, and Shanghai Children′s Medical Center, Shanghai Jiaotong University School of Medicine from January 2009 to October 2019.Results:MSP was characterized by the absent of superior limbic band of septum secundum and different degrees of the leftward deviation of septum primum, and the pulmonary veins which connected with the posterior wall of the anatomical left atrium incorporated intothe right atrium. The associated malformations included totally anomalous (7 cases) and partially anomalous (1 case) pulmonary venous drainage directly to the right atrium. Six of 8 cases were diagnosed correctly. In the remaining 2 cases, 1 case misdiagnosed as single atrium, and the other case misdiagnosed as cor triatriatum.Conclusions:MSP could be diagnosed accurately by Doppler echocardiography. This malformation should be distinguished from single atrium and cor triatriatum.

Objective:To review the imaging characteristics and evaluate the diagnostic value of Doppler echocardiography for congenital pseudoaneurysm of the mitral-aortic intervalvular fibrosa (PMAIVF).Methods:Between June 2008 and January 2020, 4 patients with PMAIVF were diagnosed by CTA, MRI and operative findings in Shanghai Children′s Medical Center and Children′s Hospital of Soochow University. The echocardiographic characteristics were analyzed retrospectively in these children.Results:PMAIVF was characterized by a pulsatile echo-free sac that expanded in systole and collapsed in diastole with to-and-fro blood flow on color and pulsed-wave Doppler echocardiography between the mitral leaflet and the aortic annulus. Three cases were diagnosed correctly, and 1 case was misdiagnosed as left atrial mass.Conclusions:PMAIVF can be diagnosed accurately by Doppler echocardiography, but it is prone to be misdiagnosed and must be distinguished from aortic root abscess, atrial mass and coronary artery fistula.

To review the imaging characteristics and evaluate the diagnostic value of echocardiography for congenital double‐chambered left ventricle ( DCLV ) in children , and improve the diagnostic accuracy of initial echocardiography . Methods Doppler echocardiography was performed and these images were compared retrospectively with operative and computed tomography angiography findings in 8 children with DCLV . Results DCLV was characterized by the presence of a main left ventricular chamber and an auxiliary chamber seperated by abnormally hypertrophic muscle and/or fiber bundles . Six cases were diagnosed with type A ,and 2 cases with type B by Li Jun′s classification . T he associated malformations included ventricular septal defect ( 3 cases ) ,mitral regurgitation ( 2 cases ) ,mitral valve stenosis ( 1 case) . Six of 8 cases( 75 .0% ) were diagnosed correctly using Doppler echocardiography ,in the remaining 2 cases ( 25 .0% ) ,1 case was missed ,1 case misdiagnosed as left ventricular diverticulum . Conclusions DCLV could be correctedly diagnosed by Doppler echocardiography . This malformation should be differentiated from left ventricular diverticulum , left ventricular aneurysm , left ventricular non‐compaction ,and ventricular septal defect .