Liu Zhen-feng,Wang Guo-lin,Dong Meng-jie,Jin Jian-wen,Li Jia-jun,Zhang Qian,Zhao Kui,Yang Shu-ye,Lin Xiang-tong
The preparation of 10-(2-[ 18 F]fluoroethoxy)-20( S )-camptothecin, a potential positron emission tomography tracer for the imaging of topoisomerase I in cancers, is described. 10-(2-[ 18 F]Fluoroethoxy)-20( S )-camptothecin was synthesized by the [ 18 F]fluoroalkylation of the corresponding hydroxy precursor molecule with 2-[ 18 F]fluoroethyl bromide ([ 18 F]FEtBr) in dimethylsulfoxide (DMSO) at 55 °C for 20 min; this was followed by purification using high performance liquid chromatography (HPLC) with a total preparation time of 60 min. The overall radiochemical yield was approximately 5.4–12 % (uncorrected), and the radiochemical purity was above 96 %.
Enhancing the accumulation and retention of small-molecule probes in tumors is an important way to achieve accurate cancer diagnosis and therapy. Enzyme-stimulated macrocyclization of small molecules possesses great potential for enhanced positron emission tomography (PET) imaging of tumors. Herein, we reported an 18F-labeled radiotracer [18F]AlF-RSM for legumain detection in vivo. The tracer was prepared by a one-step aluminum-fluoride-restrained complexing agent ([18F]AlF-RESCA) method with high radiochemical yield (RCY) (88.35 ± 3.93%) and radiochemical purity (RCP) (>95%). More notably, the tracer can be transformed into a hydrophobic macrocyclic molecule under the joint action of legumain and reductant. Simultaneously, the tracer could target legumain-positive tumors and enhance accumulation and retention in tumors, resulting in the amplification of PET imaging signals. The enhancement of radioactivity enables PET imaging of legumain activity with high specificity. We envision that, by combining this highly efficient 18F-labeled strategy with our intramolecular macrocyclization reaction, a range of radiofluorinated tracers can be designed for tumor PET imaging and early cancer diagnosis in the future.
The real-time, accurate understanding of the biodistribution of transplanted therapeutic cells is critical for their development and application. Positron emission tomography (PET) imaging has the potential to realize the noninvasive and quantitative evaluation of the spatial-temporal distribution of transplanted cells due to its unlimited tissue-penetration depth and quantitative capabilities, but its utility is limited by various shortcomings of existing imaging strategies or probes, such as the short half-life of the commonly used radioisotope fluorine-18 ( 18 F) and the interference of high nonspecific background signals to the exact localization and quantification of target cells. Here, we describe a new strategy for the long-term PET tracking and real-time quantitative analysis of transplanted cells based on a tetrazine-bearing, 18 F-labeled ultrasmall rare-earth nanoparticle probe (Tz-[ 18 F]NaGdF 4 ) capable of labeling trans-cyclooctene (TCO) pretagged T lymphocytes via a bioorthogonal reaction at any point after their transplantation. The ultrasmall Tz-[ 18 F]NaGdF 4 is readily prepared and characterized by rapid renal clearance and low nonspecific accumulation in major organs. The specific reaction between the Tz-[ 18 F]NaGdF 4 probe and pretagged cells under physiological conditions enabled the specific PET imaging of target cells with low background in situ , and the measured PET image-derived standardized uptake value linearly and positively correlated with the number of pretagged T lymphocytes retained in tissues, ensuring their accurate quantification based on real-time PET signals. Therefore, the bioorthogonal reaction-based Tz-[ 18 F]NaGdF 4 -PET represents a useful tool for the long-term tracking and real-time quantification of transplanted cells in vivo .
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