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.

The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

Objective To evaluate the harmfulness of micro-miniature unmanned aerial vehicles (UAV) to human body, especially to head caused by accidental uncontrolled crash. Methods The dynamic numerical simulation analysis was carried out by using ABAQUS software. The free-falling UAV was simplified in different geometric shapes to impact human head and the damage degree of human head caused by the impact was analyzed. Based on the biological tissue performance parameters, human head and neck was simplified as a mass-spring system and the head was modeled with actual skin texture. Results When the UAV fell from 10 m with weight of 0.5 kg, the abbreviated injury scale (AIS) of the disc-shaped UAV was 1.04, and the AIS of the corn-shaped and sphere-shaped UVA were 1.95 and 2.48. For the UAV with the same geometric shape, as the mass and the falling height increased, both impact acceleration of the head and the AIS increased. When the UAV impacted human head at different angles, the disc-shaped UAV exhibited the smallest impact acceleration, AIS and damage degree. The corn-shaped and sphere-shaped UVAs had small differences in impact acceleration and AIS, but their damage degrees were large. Conclusions When the uncontrolled micro-miniature UAV impacts human head, the mass, height or contact shape of the UAV have a significant influence on the damage degree of human head.