Immuno-PET/CT Imaging of Trop2 with [ 18 F]AlF-RESCA-T4 Differentiates Lung Cancer from Inflammation.

Autor:	Huang W; Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China., Cao M; Department of Thoracic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Wu Y; Department of Nuclear Medicine and PET Center, Huashan Hospital, Fudan University, Shanghai, China., Zhang Y; Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China., An S; Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China., Pan X; Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China., Zhou X; Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China., Shao H; Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China., Guan Y; Department of Nuclear Medicine and PET Center, Huashan Hospital, Fudan University, Shanghai, China., Huang G; Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China., Gelardi F; Università Vita-Salute San Raffaele, Milan, Italy; and.; Nuclear Medicine Department, IRCCS San Raffaele, Milano, Italy., Chiti A; Università Vita-Salute San Raffaele, Milan, Italy; and.; Nuclear Medicine Department, IRCCS San Raffaele, Milano, Italy., Xie F; Department of Nuclear Medicine and PET Center, Huashan Hospital, Fudan University, Shanghai, China., Liu J; Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China; wwei@shsmu.edu.cn ljjsh@sjtu.edu.cn., Wei W; Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China; wwei@shsmu.edu.cn ljjsh@sjtu.edu.cn.
Jazyk:	angličtina
Zdroj:	Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2024 Dec 03; Vol. 65 (12), pp. 1904-1910. Date of Electronic Publication: 2024 Dec 03.
DOI:	10.2967/jnumed.124.268751
Abstrakt:	Immuno-PET/CT imaging, a branch of molecular imaging, can noninvasively and specifically visualize biomarker expression across the body. Trophoblast cell surface antigen 2 (Trop2) is a pan-cancer biomarker and plays a crucial role in tumorigenesis through multiple signaling pathways. The study aims to develop and translate novel Trop2 single-domain antibody (sdAb) tracers for clinical use. Methods: Two sdAbs (i.e., His-tagged T4 and His-tag-free RT4) are recombinantly expressed in Chinese hamster ovary cells. The purities and binding kinetics are determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis, high-performance liquid chromatography, and surface plasmon resonance assays. The AlF restrained complexing agent (RESCA) method is applied to develop 18 F-labeled sdAb tracers ([ 18 F]AlF-RESCA-T4 and [ 18 F]AlF-RESCA-RT4), followed by thorough preclinical imaging and blocking studies on tumor-bearing mice and a pilot clinical trial evaluating the clinical imaging safety and feasibility of [ 18 F]AlF-RESCA-T4 immuno-PET/CT. Results: [ 18 F]AlF-RESCA-T4 and [ 18 F]AlF-RESCA-RT4 possess high radiochemical purities. Preclinical imaging in the T3M-4 tumor model revealed prominent uptake (percentage injected dose/g) of [ 18 F]AlF-RESCA-T4 (11.13 ± 1.53, n = 4) and [ 18 F]AlF-RESCA-RT4 (8.83 ± 1.22, n = 4), which were significantly reduced by coinjection of unlabeled T4 and RT4 in blocking studies. The His-tag removal strategy further optimized the probe's in vivo pharmacokinetics and reduced renal radioactivity accumulation without significantly decreasing tumor uptake. In a pilot clinical trial, [ 18 F]AlF-RESCA-T4 immuno-PET/CT showed promising potency in annotating Trop2 expression and differentiating tumors from inflammatory diseases such as tuberculosis. Conclusion: [ 18 F]AlF-RESCA-T4 and [ 18 F]AlF-RESCA-RT4 can specifically annotate Trop2 expression. Clinical [ 18 F]AlF-RESCA-T4 immuno-PET/CT imaging can screen patients for Trop2-targeted therapies and differentiate lung inflammation from cancer. (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)
Databáze:	MEDLINE
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