First-in-human validation of enzymolysis clearance strategy for decreasing renal radioactivity using modified [68Ga]Ga-HER2 Affibody

Zhang, Mingru; Kang, Fei; Xing, Tong; Wang, Junling; Ma, Taoqi; Li, Guiyu; Quan, Zhiyong; Yang, Weidong; Chen, Xiaoyuan; Wang, Jing

doi:10.1007/s00259-023-06584-8

Cited by 3 publications

(2 citation statements)

References 35 publications

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“…Introducing a cleavable linker, such as MVK, might be beneficial to improve the phenomenon. 34 It appeared that the performance of the probe might not be perfect. The tumor uptake and tumor-to-background contrast need to be improved.…”

Section: ■ Discussionmentioning

confidence: 99%

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Synthesis and Characterization of a Novel PET Tracer for Noninvasive Evaluation of FGL1 Status in Tumors

Tan,

Ding,

Pan

et al. 2024

Mol. Pharmaceutics

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Fibrinogen-like protein 1 (FGL1) is a potential novel immune checkpoint target for malignant tumor diagnosis and therapy. Accurate detection of FGL1 levels in tumors via noninvasive PET imaging might be beneficial for managing the disease. To achieve this, multiple FGL1-targeting peptides (FGLP) were designed, and a promising candidate, 68 Ga-NOTA-FGLP2, was identified through a high-throughput screening approach using microPET imaging of 68 Ga-labeled peptides. Subsequent in vitro cell experiments showed that uptake values of 68 Ga-NOTA-FGLP2 in FGL1 positive Huh7 tumor cells were significantly higher than those in FGL1 negative U87 MG tumor cells. Further microPET imaging showed that the Huh7 xenografts were clearly visualized with a favorable contrast. ROI analysis showed that the uptake values of the tracer in Huh7 xenografts were 2.63 ± 0.07% ID/g at 30 min p.i.. After treatment with an excess of unlabeled FGLP2, the tumor uptake significantly decreased to 0.54 ± 0.05% ID/g at 30 min p.i.. Moreover, the uptake in U87 MG xenografts was 0.44 ± 0.06% ID/g at the same time point. The tracer was excreted mainly through the renal system. 18 F-FDG PET imaging was also performed in mice bearing Huh7 and U87 MG xenografts, respectively. However, there was no significant difference in the uptake between the tumors with different FGL1 expressions. Preclinical data indicated that 68 Ga-NOTA-FGLP2 might be a suitable radiotracer for in vivo noninvasive visualization of tumors with abundant expression of FGL1. Further investigation of 68 Ga-NOTA-FGLP2 for tumor diagnosis and therapy is undergoing.

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Section: ■ Discussionmentioning

confidence: 99%

“…An enzymolysis clearance strategy has proved to be an effective way to reduce renal radioactivity in mice. Introducing a cleavable linker, such as MVK, might be beneficial to improve the phenomenon …”

Section: Discussionmentioning

confidence: 99%

Synthesis and Characterization of a Novel PET Tracer for Noninvasive Evaluation of FGL1 Status in Tumors

Tan,

Ding,

Pan

et al. 2024

Mol. Pharmaceutics

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New tactics in the design of theranostic radiotracers

Berton,

Klingler,

Prytuliak

et al. 2024

npj Imaging

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In the context of molecularly targeted radiotherapy, dosimetry concerns in off-target tissues are a major limitation to the more wide-spread application of radiopharmaceuticals to treat diseases like cancer. Reducing off-target accumulation of radionuclides in background tissues, whilst maintaining high and specific uptake in disease sites and improving the therapeutic window, requires rethinking common radiotracer design concepts. This article explores ways in which innovative radiotracer chemistry (the making and breaking of bonds) is used to modify interactions with the host organism to control excretion profiles and dosimetry at the tissue-specific level.

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The diagnostic value of 68Ga-NOTA-MAL-Cys-MZHER2:342 PET/CT imaging for HER2-positive lung adenocarcinoma

Li,

Wang,

Zhu

et al. 2024

Front. Med.

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BackgroundThe human epidermal growth factor receptor 2 gene (HER2) has been identified as a potential therapeutic target in lung adenocarcinoma (LUAD). Non-invasive positron emission tomography (PET) imaging provides a reliable strategy for in vivo determination of HER2 expression through whole-body detection of abnormalities. The PET tracer 68Ga-NOTA-MAL-Cys-MZHER2:342 has shown promising results for HER2-positive breast and gastric cancers. This study aims to evaluate the performance of 68Ga-NOTA-MAL-Cys-MZHER2:342in vitro and in vivo models and in clinical patients with HER2-positive LUAD.MethodsNOTA-MAL-Cys-MZHER2:342 was synthesized and labeled with 68Ga. Cell uptake, cell binding ability, and stability studies of 68Ga-NOTA-MAL-Cys-MZHER2:342 were assessed both in the Calu-3 lung cancer (LC) cell line and normal mice. In vivo assessment in tumor-bearing mice was conducted using microPET imaging and biodistribution experiments. Additionally, preliminary PET/CT imaging analysis was performed on HER2-positive LC patients.Results68Ga-NOTA-MAL-Cys-MZHER2:342 was prepared with a radiochemical purity (RCP) exceeding 95%. The tracer demonstrated high cell uptake in HER2-overexpressing Calu-3 cells, with an IC50 of 158.9, an adequate 1.73 nM. Good stability was exhibited both in vitro and in vivo. MicroPET imaging of Calu-3-bearing mice revealed high tumor uptake and notable tumor-to-background ratios. Positive outcomes were also observed in two HER2-positive LUAD patients.Conclusion68Ga-NOTA-MAL-Cys-MZHER2:342 demonstrated satisfactory stability, sensitivity, and specificity. These findings suggest that 68Ga-NOTA-MAL-Cys-MZHER2:342 PET/CT imaging provides a novel tool for non-invasive visual assessment of HER2 expression in LUAD patients.

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First-in-human validation of enzymolysis clearance strategy for decreasing renal radioactivity using modified [68Ga]Ga-HER2 Affibody

Cited by 3 publications

References 35 publications

Synthesis and Characterization of a Novel PET Tracer for Noninvasive Evaluation of FGL1 Status in Tumors

Synthesis and Characterization of a Novel PET Tracer for Noninvasive Evaluation of FGL1 Status in Tumors

New tactics in the design of theranostic radiotracers

The diagnostic value of 68Ga-NOTA-MAL-Cys-MZHER2:342 PET/CT imaging for HER2-positive lung adenocarcinoma

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