Search

Since the speed that the $p$ th moment of an output signal norm tends to 0 can be used to measure the quality of the output signal, the stability of the $p$ th moment of complex networks has been widely concerned. This article studies fixed-time synchronization in the $p$ th moment for time-varying delay stochastic multilayer networks, where fixed-time synchronization of multilayer networks is realized by using nonlinear feedback or delay feedback, and the concrete expression of fixed settling time is evaluated. Compared with some existing fixed-time control methods, the optimal combination relationship between the exponential power of fixed-time controllers and the $p$ th moment is given, and the designed controllers are continuous function. Finally, the effectiveness of the method is verified by numerical simulations. [ABSTRACT FROM AUTHOR]

Cancer-associated fibroblasts (CAFs) are crucial components of the tumor microenvironment. Fibroblast activation protein (FAP) is overexpressed in CAFs. FAP-targeted molecular imaging agents, including the FAP inhibitors (FAPIs) 04 and 46, have shown promising results in tumor diagnosis. However, these molecules have a relatively short tumor-retention time for peptide-targeted radionuclide therapy applications. We aimed to design a 68 Ga-labeled FAPI dimer, 68 Ga-DOTA-2P(FAPI) 2 , to optimize the pharmacokinetics and evaluate whether this form is more effective than its monomeric analogs. Methods: 68 Ga-DOTA-2P(FAPI) 2 was synthesized on the basis of the quinoline-based FAPI variant (FAPI-46), and its binding properties were assayed in CAFs. Preclinical pharmacokinetics were determined in FAP-positive patient-derived xenografts using small-animal PET and biodistribution experiments. The effective dosimetry of 68 Ga-DOTA-2P(FAPI) 2 was evaluated in 3 healthy volunteers, and PET/CT imaging of 68 Ga-FAPI-46 and 68 Ga-DOTA-2P(FAPI) 2 was performed on 3 cancer patients. Results: 68 Ga-DOTA-2P(FAPI) 2 was stable in phosphate-buffered saline and fetal bovine serum for 4 h. The FAPI dimer showed high affinity and specificity for FAP in vitro and in vivo. The tumor uptake of 68 Ga-DOTA-2P(FAPI) 2 was approximately 2-fold stronger than that of 68 Ga-FAPI-46 in patient-derived xenografts, whereas healthy organs showed low tracer uptake and fast body clearance. The effective dose of 68 Ga-DOTA-2P(FAPI) 2 was 1.19E-02 mSv/MBq, calculated using OLINDA. Finally, the PET/CT scans of the 3 cancer patients revealed higher intratumoral uptake of 68 Ga-DOTA-2P(FAPI) 2 than of 68 Ga-FAPI-46 in all tumor lesions (SUV max , 8.1-39.0 vs. 1.7-24.0, respectively; P < 0.001). Conclusion: 68 Ga-DOTA-2P(FAPI) 2 has increased tumor uptake and retention properties compared with 68 Ga-FAPI-46, and it could be a promising tracer for both diagnostic imaging and targeted therapy of malignant tumors with positive expression of FAP., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)