Imaging early-stage metastases using an (18)F-labeled VEGFR-1-specific single chain VEGF mutant Journal Article
| Authors: | Mason, C. A.; Carter, L. M.; Mandleywala, K.; Demetrio de Souza Franca, P.; Meyer, J. P.; Mamun, T.; Backer, J. M.; Backer, M. V.; Reiner, T.; Lewis, J. S. |
| Article Title: | Imaging early-stage metastases using an (18)F-labeled VEGFR-1-specific single chain VEGF mutant |
| Abstract: | Purpose: Metastatic breast cancer is the second leading cause of cancer-related death in women. The 5-year survival rate for metastatic breast cancer has remained near 26.9 % for over a decade. The recruitment of hematopoietic stem cells with high expression of the vascular endothelial growth factor receptor 1 (VEGFR-1) has been implicated in early stages of metastasis formation. We propose the use of an 18F-labeled single-chain version of VEGF121, re-engineered to be selective for VEGFR-1 (scVR1), as a positron emission tomography (PET) imaging agent to non-invasively image early-stage metastases. Procedures: scVR1 was 18F-labeled via a biorthogonal click reaction between site-specifically trans-cyclooctene functionalized scVR1 and an Al18F labeled tetrazine-NODA (1,4,7-triazacyclononane-1,4-diiacetic acid). The [18F]AlF-NODA-scVR1 was purified using a PD10 column and subsequently analyzed on HPLC to determine radiochemical purity. Animal experiments were performed in 6–8-week-old female BALB/c mice bearing orthotopic primary 4T1 breast tumors or 4T1 metastatic lesions. The [18F]AlF-NODA-scVR1 tracer was administered via tail vein injection; PET imaging and ex vivo analysis was performed 2 h post-injection. Results: The [18F]AlF-NODA-scVR1 was prepared with a 98.2 ± 1.5 % radiochemical purity and an apparent molar activity of 7.5 ± 1.2 GBq/μmol. The specific binding of scVR1 to VEGFR-1 was confirmed via bead-based assay. The ex vivo biodistribution showed tumor uptake of 3.5 ± 0.5 % ID/g and was readily observable in PET images. Metastasis formation was detected with [18F]AlF-NODA-scVR1 tracer showing colocalization with bioluminescent imaging as well as ex vivo autoradiography and immunofluorescent staining of VEGFR-1. Conclusions: The diagnostic capabilities of the [18F]AlF-NODA-scVR1 PET tracer was confirmed in both orthotopic and metastatic murine cancer models. These results support the potential use of [18F]AlF-NODA-scVR1 as a PET tracer that could image metastases, providing clinicians with an additional tool to assess a patient’s need for adjuvant therapies. © 2020, World Molecular Imaging Society. |
| Keywords: | immunofluorescence; lung metastasis; pet imaging; metastatic breast cancer; autoradiography; radiochemistry; tumor microenvironment; vegfr-1; metastatic niche |
| Journal Title: | Molecular Imaging and Biology |
| Volume: | 23 |
| Issue: | 3 |
| ISSN: | 1536-1632 |
| Publisher: | Springer |
| Date Published: | 2021-06-01 |
| Start Page: | 340 |
| End Page: | 349 |
| Language: | English |
| DOI: | 10.1007/s11307-020-01555-z |
| PUBMED: | 33156495 |
| PROVIDER: | scopus |
| PMCID: | PMC8099920 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 June 2021 -- Source: Scopus |
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