In Vivo Distribution and Therapeutic Efficacy of Radioiodine-Labeled pH-Low Insertion Peptide Variant 3 in a Mouse Model of Breast Cancer
Purpose. Extracellular acidity is a marker of highly aggressive breast cancer (BC). pH-low insertion peptides (pHLIPs) target the acidic tumor microenvironment. This study evaluates the distribution and therapeutic efficacy of radioiodine-labeled pHLIP variant 3 (Var3) in a mouse model of BC. Method...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2022-01-01
|
| Series: | Molecular Imaging |
| Online Access: | http://dx.doi.org/10.1155/2022/7456365 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850082838195470336 |
|---|---|
| author | Min Zhang Yue Xi Hong Chen Wangxi Hai Biao Li |
| author_facet | Min Zhang Yue Xi Hong Chen Wangxi Hai Biao Li |
| author_sort | Min Zhang |
| collection | DOAJ |
| description | Purpose. Extracellular acidity is a marker of highly aggressive breast cancer (BC). pH-low insertion peptides (pHLIPs) target the acidic tumor microenvironment. This study evaluates the distribution and therapeutic efficacy of radioiodine-labeled pHLIP variant 3 (Var3) in a mouse model of BC. Methods. The binding of fluorescein isothiocyanate (FITC)- or radioiodine-125 (125I) labeled Var3-pHLIP to MDA-MB-231, 4T1, and SK-BR-3 BC cell lines under different pH values was evaluated in vitro. The distribution of 125I-labeled Var3-pHLIP and wild-type- (WT-) pHLIP in tumor-bearing mice was analyzed in vivo using micro-SPECT/CT imaging. The therapeutic efficacy of radioiodine-131 (131I)-labeled Var3-pHLIP in MDA-MB-231 xenografts was evaluated by relative tumor volume measurement and immunohistochemical analysis. Results. The binding ability of FITC- or 125I-labeled Var3-pHLIP to tumor cells increased with the decrease in pH. The tumor-to-background ratio of 125I-Var3-pHLIP in BC xenografts showed the best imaging contrast at 24 h or 48 h postinjection. The uptake of 125I-Var3-pHLIP in MDA-MB-231 xenografts at 2 h postinjection was significantly higher than that of 125I-WT-pHLIP (3.76±0.37 vs. 2.87±0.60%ID/g, p=0.046). The relative tumor volume in MDA-MB-231 xenografts was significantly lower in the 131I-Var3-pHLIP-treated group than in the groups treated with Var3-pHLIP (p=0.027), 131I (p=0.001), and saline (p<0.001). The 131I-Var 3-pHLIP group presented a lower expression of Ki67 and a higher expression of caspase 3. Conclusion. Radioiodine-labeled Var3-pHLIP effectively targeted BC cells in an acidic environment and inhibited the growth of MDA-MB-231 xenografts by ionizing radiation. |
| format | Article |
| id | doaj-art-4f68446e6ad94daa8b52dbf1f504f49a |
| institution | DOAJ |
| issn | 1536-0121 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj-art-4f68446e6ad94daa8b52dbf1f504f49a2025-08-20T02:44:27ZengSAGE PublishingMolecular Imaging1536-01212022-01-01202210.1155/2022/7456365In Vivo Distribution and Therapeutic Efficacy of Radioiodine-Labeled pH-Low Insertion Peptide Variant 3 in a Mouse Model of Breast CancerMin Zhang0Yue Xi1Hong Chen2Wangxi Hai3Biao Li4Department of Nuclear MedicineDepartment of Nuclear MedicineDepartment of Nuclear MedicineDepartment of Nuclear MedicineDepartment of Nuclear MedicinePurpose. Extracellular acidity is a marker of highly aggressive breast cancer (BC). pH-low insertion peptides (pHLIPs) target the acidic tumor microenvironment. This study evaluates the distribution and therapeutic efficacy of radioiodine-labeled pHLIP variant 3 (Var3) in a mouse model of BC. Methods. The binding of fluorescein isothiocyanate (FITC)- or radioiodine-125 (125I) labeled Var3-pHLIP to MDA-MB-231, 4T1, and SK-BR-3 BC cell lines under different pH values was evaluated in vitro. The distribution of 125I-labeled Var3-pHLIP and wild-type- (WT-) pHLIP in tumor-bearing mice was analyzed in vivo using micro-SPECT/CT imaging. The therapeutic efficacy of radioiodine-131 (131I)-labeled Var3-pHLIP in MDA-MB-231 xenografts was evaluated by relative tumor volume measurement and immunohistochemical analysis. Results. The binding ability of FITC- or 125I-labeled Var3-pHLIP to tumor cells increased with the decrease in pH. The tumor-to-background ratio of 125I-Var3-pHLIP in BC xenografts showed the best imaging contrast at 24 h or 48 h postinjection. The uptake of 125I-Var3-pHLIP in MDA-MB-231 xenografts at 2 h postinjection was significantly higher than that of 125I-WT-pHLIP (3.76±0.37 vs. 2.87±0.60%ID/g, p=0.046). The relative tumor volume in MDA-MB-231 xenografts was significantly lower in the 131I-Var3-pHLIP-treated group than in the groups treated with Var3-pHLIP (p=0.027), 131I (p=0.001), and saline (p<0.001). The 131I-Var 3-pHLIP group presented a lower expression of Ki67 and a higher expression of caspase 3. Conclusion. Radioiodine-labeled Var3-pHLIP effectively targeted BC cells in an acidic environment and inhibited the growth of MDA-MB-231 xenografts by ionizing radiation.http://dx.doi.org/10.1155/2022/7456365 |
| spellingShingle | Min Zhang Yue Xi Hong Chen Wangxi Hai Biao Li In Vivo Distribution and Therapeutic Efficacy of Radioiodine-Labeled pH-Low Insertion Peptide Variant 3 in a Mouse Model of Breast Cancer Molecular Imaging |
| title | In Vivo Distribution and Therapeutic Efficacy of Radioiodine-Labeled pH-Low Insertion Peptide Variant 3 in a Mouse Model of Breast Cancer |
| title_full | In Vivo Distribution and Therapeutic Efficacy of Radioiodine-Labeled pH-Low Insertion Peptide Variant 3 in a Mouse Model of Breast Cancer |
| title_fullStr | In Vivo Distribution and Therapeutic Efficacy of Radioiodine-Labeled pH-Low Insertion Peptide Variant 3 in a Mouse Model of Breast Cancer |
| title_full_unstemmed | In Vivo Distribution and Therapeutic Efficacy of Radioiodine-Labeled pH-Low Insertion Peptide Variant 3 in a Mouse Model of Breast Cancer |
| title_short | In Vivo Distribution and Therapeutic Efficacy of Radioiodine-Labeled pH-Low Insertion Peptide Variant 3 in a Mouse Model of Breast Cancer |
| title_sort | in vivo distribution and therapeutic efficacy of radioiodine labeled ph low insertion peptide variant 3 in a mouse model of breast cancer |
| url | http://dx.doi.org/10.1155/2022/7456365 |
| work_keys_str_mv | AT minzhang invivodistributionandtherapeuticefficacyofradioiodinelabeledphlowinsertionpeptidevariant3inamousemodelofbreastcancer AT yuexi invivodistributionandtherapeuticefficacyofradioiodinelabeledphlowinsertionpeptidevariant3inamousemodelofbreastcancer AT hongchen invivodistributionandtherapeuticefficacyofradioiodinelabeledphlowinsertionpeptidevariant3inamousemodelofbreastcancer AT wangxihai invivodistributionandtherapeuticefficacyofradioiodinelabeledphlowinsertionpeptidevariant3inamousemodelofbreastcancer AT biaoli invivodistributionandtherapeuticefficacyofradioiodinelabeledphlowinsertionpeptidevariant3inamousemodelofbreastcancer |