Search on Kit Lam Lab - UC Davis's publications

Despite advances in cancer treatment over the past few decades metastatic disease remains the primary cause of morbidity and mortality Recent reports suggest the formation of a premetastatic niche before the metastatic cascade where niche is defined as the microenvironment for tumor cells to be able to engraft and proliferate at secondary sites Bone marrow-derived BMD cells that express vascular endothelial growth factor receptor-1 and very late antigen-4 VLA-4 have been shown to arrive at sites of metastasis to form a receptive environment for tumor cells Here we describe experiments toward imaging of VLA-4-positive BMD cells using a high-affinity PET probe 64 Cu-labeled 11-bis carboxymethyl -1 4 8 11-tetraazabicyclo 6 6 2 hexadecane CB-TE2A -LLP2A VLA-4-negative MDA-MB-231 firefly luciferase fluc human breast tumor cells were injected intraarterially in the left ventricle in nude mice Tumor metastasis in mice was monitored for 30 d by bioluminescence imaging and small-animal PET CT Small-animal PET images were collected 2 h after mice were injected in the tail vein with 64 Cu-CB-TE2A-LLP2A 5 6-11 1 MBq 150-300 Ci specific activity 400 Ci g Cellular uptake of 64 Cu-CB-TE2A-LLP2A was determined in VLA-4-positive B16F10 mouse melanoma cells and VLA-4-negative MDA-MB-231 fluc human breast cancer tumor cells Biodistribution experiments in nude mice bearing VLA-4-positive B16F10 subcutaneous tumors in the flank were conducted to validate targeting of VLA-4-positive cells in vivo Uptake of 64 Cu-CB-TE2A-LLP2A was higher in VLA-4-positive human melanoma B16F10 cells than in VLA-4-negative MDA-MB-231 cells P 0 05 In B16F10 tumor-bearing mice 64 Cu-CB-TE2A-LLP2A had high uptake in the VLA-4-rich organs marrow spleen and tumor 11 26 2 59 8 36 2 15 and 3 09 0 58 injected dose g respectively Cumulative standardized uptake value data from 2 independent studies n 7 and 8 mice on nude mice implanted with VLA-4-negative MDA-MB-231 fluc human breast tumor cells suggested an influx of VLA-4-positive BMD cells that corresponded to metastasis P 0 05 Immunohistochemical analysis and flow cytometry also showed upregulation of VLA-4-positive cell clusters and BMD cells at the metastatic sites providing evidence for noninvasive imaging of BMD cells in the premetastatic niche The results of the study demonstrated the potential of PET with VLA-4-targeted 64 Cu-CB-TE2A-LLP2A to visualize BMD cell reorganization and expansion noninvasively in vivo

Publication search

Molecular imaging of very late antigen-4 (α4β1 integrin) in the premetastatic niche.