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Use of Labelled tLyP-1 as a Novel Ligand Targeting the NRP Receptor to Image Glioma.

Wu HB, Wang Z, Wang QS, Han YJ, Wang M, Zhou WL, Li HS - PLoS ONE (2015)

Bottom Line: The in vivo biodistribution of 18F-tLyP-1 was also determined by microPET/CT.In vitro, FAM-tLyP-1 was strongly taken up by U87MG cells at very low concentrations (1 μM).Taken together, our results suggest that tLyP-1 could be developed as a novel fluorescent or radio labelled tracer for imaging glioma.

View Article: PubMed Central - PubMed

Affiliation: NanFang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.

ABSTRACT

Background: Neuropilin (NRP) receptors are overexpressed in glioma tumor tissue, and therefore may be a potential target for imaging markers. We investigated whether labelled tLyP-1, an NRP targeting peptide, could be used as the targeting ligand for developing reagents for imaging glioma tumors.

Methods: The tLyP-1 peptide (CGNKRTR) was labeled with 5-carboxyfluorescein (FAM) or 18F-fluoride. A control peptide (MAQKTSH) was also labeled with FAM. The in vitro binding between FAM-tLyP-1 and U87MG cells and in vivo biodistribution of FAM-tLyP-1 in a U87MG glioblastoma xenograft model (nude mouse) were determined. The in vivo biodistribution of 18F-tLyP-1 was also determined by microPET/CT.

Results: In vitro, FAM-tLyP-1 was strongly taken up by U87MG cells at very low concentrations (1 μM). In vivo, FAM-tLyP-1 accumulated in glioma (U87MG) tumors, but uptake was minimal in the normal brain tissue 1 h after administration. The distribution of FAM-tLyP-1 in the tumor tissue was consistent with expression of NRP1. The tumor/brain fluorescence intensity ratio in mice treated with FAM-tLyP-1 was significantly higher than the control FAM-labeled peptide 1 h after administration (3.44 ± 0.83 vs. 1.32 ± 0.15; t = 5.547, P = 0.001). Uptake of FAM-tLyP-1 in glioma tumors could be blocked by administering an excess of non-conjugated tLyP-1 peptide. [Lys4] tLyP-1 was labeled with 18F to synthesis a PET (18F-tLyP-1). MicroPET/CT imaging showed the tumor was visualized clearly with a high tumor/brain radiolabel ratio at 60 min (2.69 ± 0.52) and 120 min (3.11 ± 0.25).

Conclusion: Taken together, our results suggest that tLyP-1 could be developed as a novel fluorescent or radio labelled tracer for imaging glioma.

No MeSH data available.


Related in: MedlinePlus

Uptake of FAM-tLyP-1 in tumor and normal organ tissues.(A) Tumor and normal organ tissues were removed and examined for fluorescence 1 h after FAM-tLyP-1 was intravenously injected into U87MG tumor bearing mice. (B) Uptake of FAM-tLyP-1 and FAM-control peptide in tumor and normal brain tissue.
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pone.0137676.g004: Uptake of FAM-tLyP-1 in tumor and normal organ tissues.(A) Tumor and normal organ tissues were removed and examined for fluorescence 1 h after FAM-tLyP-1 was intravenously injected into U87MG tumor bearing mice. (B) Uptake of FAM-tLyP-1 and FAM-control peptide in tumor and normal brain tissue.

Mentions: To assess whether FAM-tLyP-1 had a sufficient signal to background ratio in vivo, we assessed the intensity of the green fluorescence in tumor tissue and normal tissue from individual organs in nude mice with U87MG tumors. One (1) hour after administration of the FAM-tLyP-1 the fluorescence intensity of FAM-tLyP-1 in the tumor was very high, compared to minimal fluorescence in the normal brain tissue (Fig 4A). The fluorescence intensity in the tumor was significantly greater than the normal brain with a tumor/brain ratio of 3.44 ± 0.83 (Table 1). The T/NT fluorescence ratio of the FAM-control peptide was 1.32 ± 0.15 in the brain after 1 h (Fig 4B), and was significantly lower than FAM-tLyP-1 (t = -5.547, P = 0.001; Table 1).


Use of Labelled tLyP-1 as a Novel Ligand Targeting the NRP Receptor to Image Glioma.

Wu HB, Wang Z, Wang QS, Han YJ, Wang M, Zhou WL, Li HS - PLoS ONE (2015)

Uptake of FAM-tLyP-1 in tumor and normal organ tissues.(A) Tumor and normal organ tissues were removed and examined for fluorescence 1 h after FAM-tLyP-1 was intravenously injected into U87MG tumor bearing mice. (B) Uptake of FAM-tLyP-1 and FAM-control peptide in tumor and normal brain tissue.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4580457&req=5

pone.0137676.g004: Uptake of FAM-tLyP-1 in tumor and normal organ tissues.(A) Tumor and normal organ tissues were removed and examined for fluorescence 1 h after FAM-tLyP-1 was intravenously injected into U87MG tumor bearing mice. (B) Uptake of FAM-tLyP-1 and FAM-control peptide in tumor and normal brain tissue.
Mentions: To assess whether FAM-tLyP-1 had a sufficient signal to background ratio in vivo, we assessed the intensity of the green fluorescence in tumor tissue and normal tissue from individual organs in nude mice with U87MG tumors. One (1) hour after administration of the FAM-tLyP-1 the fluorescence intensity of FAM-tLyP-1 in the tumor was very high, compared to minimal fluorescence in the normal brain tissue (Fig 4A). The fluorescence intensity in the tumor was significantly greater than the normal brain with a tumor/brain ratio of 3.44 ± 0.83 (Table 1). The T/NT fluorescence ratio of the FAM-control peptide was 1.32 ± 0.15 in the brain after 1 h (Fig 4B), and was significantly lower than FAM-tLyP-1 (t = -5.547, P = 0.001; Table 1).

Bottom Line: The in vivo biodistribution of 18F-tLyP-1 was also determined by microPET/CT.In vitro, FAM-tLyP-1 was strongly taken up by U87MG cells at very low concentrations (1 μM).Taken together, our results suggest that tLyP-1 could be developed as a novel fluorescent or radio labelled tracer for imaging glioma.

View Article: PubMed Central - PubMed

Affiliation: NanFang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.

ABSTRACT

Background: Neuropilin (NRP) receptors are overexpressed in glioma tumor tissue, and therefore may be a potential target for imaging markers. We investigated whether labelled tLyP-1, an NRP targeting peptide, could be used as the targeting ligand for developing reagents for imaging glioma tumors.

Methods: The tLyP-1 peptide (CGNKRTR) was labeled with 5-carboxyfluorescein (FAM) or 18F-fluoride. A control peptide (MAQKTSH) was also labeled with FAM. The in vitro binding between FAM-tLyP-1 and U87MG cells and in vivo biodistribution of FAM-tLyP-1 in a U87MG glioblastoma xenograft model (nude mouse) were determined. The in vivo biodistribution of 18F-tLyP-1 was also determined by microPET/CT.

Results: In vitro, FAM-tLyP-1 was strongly taken up by U87MG cells at very low concentrations (1 μM). In vivo, FAM-tLyP-1 accumulated in glioma (U87MG) tumors, but uptake was minimal in the normal brain tissue 1 h after administration. The distribution of FAM-tLyP-1 in the tumor tissue was consistent with expression of NRP1. The tumor/brain fluorescence intensity ratio in mice treated with FAM-tLyP-1 was significantly higher than the control FAM-labeled peptide 1 h after administration (3.44 ± 0.83 vs. 1.32 ± 0.15; t = 5.547, P = 0.001). Uptake of FAM-tLyP-1 in glioma tumors could be blocked by administering an excess of non-conjugated tLyP-1 peptide. [Lys4] tLyP-1 was labeled with 18F to synthesis a PET (18F-tLyP-1). MicroPET/CT imaging showed the tumor was visualized clearly with a high tumor/brain radiolabel ratio at 60 min (2.69 ± 0.52) and 120 min (3.11 ± 0.25).

Conclusion: Taken together, our results suggest that tLyP-1 could be developed as a novel fluorescent or radio labelled tracer for imaging glioma.

No MeSH data available.


Related in: MedlinePlus