Dataset Information

A proof-of-concept study on bioorthogonal-based pretargeting and signal amplify radiotheranostic strategy.

ABSTRACT:

Background

Radiotheranostics differs from the vast majority of other cancer therapies in its capacity for simultaneous imaging and therapy, and it is becoming more widely implemented. A balance between diagnostic and treatment requirements is essential for achieving effective radiotheranostics. Herein, we propose a proof-of-concept strategy aiming to address the profound differences in the specific requirements of the diagnosis and treatment of radiotheranostics.

Results

To validate the concept, we designed an s-tetrazine (Tz) conjugated prostate-specific membrane antigen (PSMA) ligand (DOTA-PSMA-Tz) for ⁶⁸Ga or ¹⁷⁷Lu radiolabeling and tumor radiotheranostics, a trans-cyclooctene (TCO) modified Pd@Au nanoplates (Pd@Au-PEG-TCO) for signal amplification, respectively. We then demonstrated this radiotheranostic strategy in the tumor-bearing mice with the following three-step procedures: (1) i.v. injection of the [⁶⁸Ga]Ga-PSMA-Tz for diagnosis; (2) i.v. injection of the signal amplification module Pd@Au-PEG-TCO; (3) i.v. injection of the [¹⁷⁷Lu]Lu-PSMA-Tz for therapy. Firstly, this strategy was demonstrated in 22Rv1 tumor-bearing mice via positron emission tomography (PET) imaging with [⁶⁸Ga]Ga-PSMA-Tz. We observed significantly higher tumor uptake (11.5 ± 0.8%ID/g) with the injection of Pd@Au-PEG-TCO than with the injection [⁶⁸Ga]Ga-PSMA-Tz alone (5.5 ± 0.9%ID/g). Furthermore, we validated this strategy through biodistribution studies of [¹⁷⁷Lu]Lu-PSMA-Tz, with the injection of the signal amplification module, approximately five-fold higher tumor uptake of [¹⁷⁷Lu]Lu-PSMA-Tz (24.33 ± 2.53% ID/g) was obtained when compared to [¹⁷⁷Lu]Lu-PSMA-Tz alone (5.19 ± 0.26%ID/g) at 48 h post-injection.

Conclusion

In summary, the proposed strategy has the potential to expand the toolbox of pretargeted radiotherapy in the field of theranostics.

SUBMITTER: Yang H

PROVIDER: S-EPMC10926607 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Publications

A proof-of-concept study on bioorthogonal-based pretargeting and signal amplify radiotheranostic strategy.

Yang Hongzhang H Zeng Xinying X Liu Jia J Li Jingchao J Li Yun Y Zhang Qinglin Q Shu Linlin L Liu Huanhuan H Wang Xueqi X Liang Yuanyuan Y Hu Ji J Huang Lumei L Guo Zhide Z Zhang Xianzhong X

Journal of nanobiotechnology 20240310 1

<h4>Background</h4>Radiotheranostics differs from the vast majority of other cancer therapies in its capacity for simultaneous imaging and therapy, and it is becoming more widely implemented. A balance between diagnostic and treatment requirements is essential for achieving effective radiotheranostics. Herein, we propose a proof-of-concept strategy aiming to address the profound differences in the specific requirements of the diagnosis and treatment of radiotheranostics.<h4>Results</h4>To valida ...[more]

PMID: 38462598

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Project description:A major concern in the care of common variable immunodeficiency (CVID) patients is the persistence of subclinical or recurrent respiratory tract infections (RRTI) despite adequate trough IgG levels, which impacts the quality of life (QoL) and morbidity. Therefore, the development of new approaches to prevent and treat infection, especially RRTI, is necessary. We conducted a clinical observational study from May, 2016 to December, 2017 in 20 CVID patients; ten of these patients had a history of RRTI and received the polybacterial preparation MV130, a trained immunity-based vaccine (TIbV) to assess its impact on their QoL and prognosis. Subjects with RRTI received MV130 for 3 months and were followed up to 12 months after initiation of the treatment. The primary endpoint was a reduction in RRTI at the end of the study. We analyzed the pharmacoeconomic impact on the RRTI group before and after immunotherapy by estimating the direct and indirect costs, and assessed CVID-QoL and cytokine profile. Specific antibody responses to the bacteria contained in MV130 were measured. The RRTI-group treated with TIbV MV130 showed a significant decrease in infection rate (p = 0.006) throughout the 12 months after initiation of the treatment. A decrease in antibiotic use and unscheduled outpatient visits was observed (p = 0.005 and p = 0.002, respectively). Significant increases in anti-pneumococcus and anti-MV130 IgA antibodies (p = 0.039 both) were detected after 12 months of MV130. Regarding the CVID QoL questionnaire, an overall decrease in the score by more than 50% was observed (p < 0.05) which demonstrated that patients experienced an improvement in their QoL. The pharmacoeconomic analysis showed that the real annual direct costs decreased up to 4 times per patient with the prophylactic intervention (p = 0.005). The sublingual administration of the TIbV MV130 significantly reduced the rate of respiratory infections, antibiotic use and unscheduled visits, while increasing specific IgA responses in CVID patients. Additionally, the CVID population felt that their QoL was improved, and a decrease in expenses derived from health care was predicted.

Dataset Information

A proof-of-concept study on bioorthogonal-based pretargeting and signal amplify radiotheranostic strategy.

Background

Results

Conclusion

Publications

A proof-of-concept study on bioorthogonal-based pretargeting and signal amplify radiotheranostic strategy.

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