Reduction of the Renal Radioactivity of <sup>111</sup>In-DOTA-Labeled Antibody Fragments with a Linkage Cleaved by the Renal Brush Border Membrane Enzymes

Suzuki, Hiroyuki; Araki, Mari; Tatsugi, Kouki; Ichinohe, Kento; Uehara, Tomoya; Arano, Yasushi

doi:10.1021/acs.jmedchem.3c00258

Cited by 6 publications

(3 citation statements)

References 45 publications

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“…This strategy was initially developed as a radioiodinated antibody Fab fragment in 1999 [136] but was difficult to apply to radiometals, with the exception of 188 Re-labeled Fab [137]. In the past decade, we succeeded in applying the renal brush border strategy to several radiometals, such as 99m Tc, 67 Ga, 64 Cu, and 111 In [138][139][140][141][142]. Although this strategy has not yet been applied to RIT, the dramatic reduction in renal radioactivity may contribute to enhanced therapeutic effects.…”

Section: Antibody Fragments and Constructsmentioning

confidence: 99%

Approaches to Reducing Normal Tissue Radiation from Radiolabeled Antibodies

Suzuki,

Kannaka,

Uehara

2024

Pharmaceuticals

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Radiolabeled antibodies are powerful tools for both imaging and therapy in the field of nuclear medicine. Radiolabeling methods that do not release radionuclides from parent antibodies are essential for radiolabeling antibodies, and practical radiolabeling protocols that provide high in vivo stability have been established for many radionuclides, with a few exceptions. However, several limitations remain, including undesirable side effects on the biodistribution profiles of antibodies. This review summarizes the numerous efforts made to tackle this problem and the recent advances, mainly in preclinical studies. These include pretargeting approaches, engineered antibody fragments and constructs, the secondary injection of clearing agents, and the insertion of metabolizable linkages. Finally, we discuss the potential of these approaches and their prospects for further clinical application.

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Section: Antibody Fragments and Constructsmentioning

confidence: 99%

Approaches to Reducing Normal Tissue Radiation from Radiolabeled Antibodies

Suzuki,

Kannaka,

Uehara

2024

Pharmaceuticals

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“…Specific and adequate accumulation of probes for imaging radiotherapy in the area of interest with robust imaging enhancements and a great safety profile should be addressed during the design step. In this context, from a chemical structure perspective, the ligands for targeting biomarkers 178 , the linkers cleavable by biomarkers 188 , 189 , the chelators for paramagnetic ions or diagnostic radionuclides 190 , and the biomarker-activatable imaging enhancement principles should be considered for the probes 191 . The basic in vivo working mechanism(s) of a certain probe type, including tumor targeting 192 , excretion 193 , and signal activation 14 , should become the cornerstone for the development of probe-mediated molecular imaging.…”

Section: Reflection and Future Perspectivementioning

confidence: 99%

Biomarker-driven molecular imaging probes in radiotherapy

Li,

Gong,

Luo

2024

Theranostics

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Background: Biomarker-driven molecular imaging has emerged as an integral part of cancer precision radiotherapy. The use of molecular imaging probes, including nanoprobes, have been explored in radiotherapy imaging to precisely and noninvasively monitor spatiotemporal distribution of biomarkers, potentially revealing tumor-killing mechanisms and therapy-induced adverse effects during radiation treatment. Methods: We summarized literature reports from preclinical studies and clinical trials, which cover two main parts: 1) Clinically-investigated and emerging imaging biomarkers associated with radiotherapy, and 2) instrumental roles, functions, and activatable mechanisms of molecular imaging probes in the radiotherapy workflow. In addition, reflection and future perspectives are proposed. Results: Numerous imaging biomarkers have been continuously explored in decades, while few of them have been successfully validated for their correlation with radiotherapeutic outcomes and/or radiation-induced toxicities. Meanwhile, activatable molecular imaging probes towards the emerging biomarkers have exhibited to be promising in animal or small-scale human studies for precision radiotherapy. Conclusion: Biomarker-driven molecular imaging probes are essential for precision radiotherapy. Despite very inspiring preliminary results, validation of imaging biomarkers and rational design strategies of probes await robust and extensive investigations. Especially, the correlation between imaging biomarkers and radiotherapeutic outcomes/toxicities should be established through multi-center collaboration involving a large cohort of patients.

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“…To minimize damage to the kidneys, the maximum tolerated dose is reduced, leading to compromised treatment efficacy. This research utilized a cleavable linker which could be recognized and cleaved by angiotensin-converting enzyme (ACE) or neprilysin to reduce kidney uptake of radiolabeled peptides and proteins. , Gustafsson et al describe the in vitro and in vivo evaluation of new long-lasting glucagon-like peptide 1 (GLP-1) derivatives labeled with Zr-89. Reduced kidney accumulation was achieved by introducing an enzymatically cleavable motif between the chelator and the peptide …”

Section: Radiopharmaceuticals For Cancer Imaging and Therapymentioning

confidence: 99%

Diagnostic and Therapeutic Radiopharmaceuticals: A “Hot” Topic

Lindsley,

Müller,

Bongarzone

2023

ACS Pharmacol. Transl. Sci.

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we attempted to capture some of the advances in the field of radiolabeled pharmaceuticals for imaging and therapy. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) radiopharmaceuticals can be used to diagnose and monitor the progression of diseases such as neurological disorders, cancer, cardiovascular disease, and infections. In addition, their use helps to guide therapeutic interventions, such as radiation therapy, pharmacological treatment, and surgery, by monitoring the effectiveness of these treatments. In light of this, Yang et al. outlined factors on target druggability for diagnostic radiopharmaceuticals. 1 Not surprisingly, more than 80% of the articles in this collection have reported radiopharmaceuticals for PET/SPECT imaging. Almost 50% of the radioligands for imaging presented in this collection were radiolabeled with fluorine-18. Research papers using other radionuclides for imaging such as carbon-11, gallium-68, indium-111, technetium-99m, zirconium-89, and copper-64 are also found in this collection.On the other hand, therapeutic radiopharmaceuticals induce pharmacological effects as a result of the radiotoxicity induced by the emission of particulate radiation. While designing a radiopharmaceutical for a therapeutic application, the choice of the appropriate radionuclide constitutes a prime determinant. In this collection, radionuclides such lutetium-177, astatine-211, and actinium-225 are among those reported in radiopharmaceuticals for therapeutic application.

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Reduction of the Renal Radioactivity of ¹¹¹In-DOTA-Labeled Antibody Fragments with a Linkage Cleaved by the Renal Brush Border Membrane Enzymes

Cited by 6 publications

References 45 publications

Approaches to Reducing Normal Tissue Radiation from Radiolabeled Antibodies

Approaches to Reducing Normal Tissue Radiation from Radiolabeled Antibodies

Biomarker-driven molecular imaging probes in radiotherapy

Diagnostic and Therapeutic Radiopharmaceuticals: A “Hot” Topic

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Reduction of the Renal Radioactivity of 111In-DOTA-Labeled Antibody Fragments with a Linkage Cleaved by the Renal Brush Border Membrane Enzymes

Cited by 6 publications

References 45 publications

Approaches to Reducing Normal Tissue Radiation from Radiolabeled Antibodies

Approaches to Reducing Normal Tissue Radiation from Radiolabeled Antibodies

Biomarker-driven molecular imaging probes in radiotherapy

Diagnostic and Therapeutic Radiopharmaceuticals: A “Hot” Topic

Contact Info

Product

Resources

About

Reduction of the Renal Radioactivity of ¹¹¹In-DOTA-Labeled Antibody Fragments with a Linkage Cleaved by the Renal Brush Border Membrane Enzymes