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. 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 F-labeled sdAb tracers ([F]AlF-RESCA-T4 and [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 [F]AlF-RESCA-T4 immuno-PET/CT. [F]AlF-RESCA-T4 and [F]AlF-RESCA-RT4 possess high radiochemical purities. Preclinical imaging in the T3M-4 tumor model revealed prominent uptake (percentage injected dose/g) of [F]AlF-RESCA-T4 (11.13 ± 1.53, = 4) and [F]AlF-RESCA-RT4 (8.83 ± 1.22, = 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, [F]AlF-RESCA-T4 immuno-PET/CT showed promising potency in annotating Trop2 expression and differentiating tumors from inflammatory diseases such as tuberculosis. [F]AlF-RESCA-T4 and [F]AlF-RESCA-RT4 can specifically annotate Trop2 expression. Clinical [F]AlF-RESCA-T4 immuno-PET/CT imaging can screen patients for Trop2-targeted therapies and differentiate lung inflammation from cancer.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2967/jnumed.124.268751 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Immuno-PET/CT Imaging of Trop2 with [F]AlF-RESCA-T4 Differentiates Lung Cancer from Inflammation.
J Nucl Med
December 2024
Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China;
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.
View Article and Find Full Text PDFCD70-Targeted Immuno-PET/CT Imaging of Clear Cell Renal Cell Carcinoma: A Translational Study.
J Nucl Med
December 2024
Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China;
The diagnosis and surveillance of clear cell renal cell carcinoma (ccRCC) remains a clinical challenge. The high and specific expression of the cluster of differentiation 70 (CD70) in ccRCC makes it a potential diagnostic and therapeutic target. We detected and analyzed CD70 expression in various renal cell carcinomas (RCCs) and normal kidneys using immunohistochemical staining.
View Article and Find Full Text PDFPreclinical imaging evaluation of a bispecific antibody targeting hPD1/CTLA4 using humanized mice.
Biomed Pharmacother
June 2024
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China; Institute of Biomedical Engineering, Peking University Shenzhen Graduate School, Shenzhen, Guangdong 518055, China. Electronic address:
Article Synopsis
- The study addresses the challenge of efficiently screening patients for responsiveness to immunotherapy in cancer treatment, specifically targeting PD1/CTLA4.
- The research involved developing a bispecific antibody (AK104) labeled with radionuclide isotopes and employing immuno-PET imaging to visualize and evaluate the therapeutic impact on PD1/CTLA4-positive T cells in humanized mouse models.
- Findings indicate that the I-AK104 antibody demonstrated high specificity and efficacy in targeting tumor-infiltrating T cells, suggesting it could be a valuable tool for identifying patients who would benefit from immunotherapy.
Long Versus Short Axial Field of View Immuno-PET/CT: Semiquantitative Evaluation for Zr-Trastuzumab.
J Nucl Med
November 2023
Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
The purpose of this study was to quantify any differences between the SUVs of Zr immuno-PET scans obtained using a PET/CT system with a long axial field of view (LAFOV; Biograph Vision Quadra) compared to a PET/CT system with a short axial field of view (SAFOV; Biograph Vision) and to evaluate how LAFOV PET scan duration affects image noise and SUV metrics. Five metastatic breast cancer patients were scanned consecutively on SAFOV and LAFOV PET/CT scanners. Four additional patients were scanned using only LAFOV PET/CT.
View Article and Find Full Text PDFProteomic Profiling of Extracellular Matrix Components from Patient Metastases Identifies Consistently Elevated Proteins for Developing Nanobodies That Target Primary Tumors and Metastases.
Cancer Res
June 2023
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts.
Unlabelled: Metastases are hard to detect and treat, and they cause most cancer-related deaths. The relative lack of therapies targeting metastases represents a major unmet clinical need. The extracellular matrix (ECM) forms a major component of the tumor microenvironment in both primary and metastatic tumors, and certain ECM proteins can be selectively and abundantly expressed in tumors.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!