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Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.

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Molecular Imaging and Contrast Agent Database (MICAD) [Internet].

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125I-Vascular endothelial growth factor-121

125I-VEGF121
, PhD
National Center for Biotechnology Information, NLM, NIH, vog.hin.mln.ibcn@dacim

Created: ; Last Update: July 6, 2007.

Chemical name:125I-Vascular endothelial growth factor-121
Abbreviated name:125I-VEGF121
Synonym:
Agent Category:Polypeptide
Target:VEGF receptors
Target Category:Receptor binding
Method of detection:SPECT, planar gamma
Source of signal:125I
Activation:No
Studies:
  • Checkbox In vitro
  • Checkbox Rodents
Click on protein, nucleotide (RefSeq), and gene for more information about VEGF.

Background

[PubMed]

Vascular endothelial growth factor (VEGF) consists of at least six isoforms of various number of amino acids (121, 145, 165, 183, 189, and 206 amino acids) produced through alternative splicing (1). VEGF121, VEGF165, and VEGF189 are the forms secreted by most cell types and are active as homodimers linked by disulfide bonds. VEGF121 does not bind to heparin like the other VEGF species (2). VEGF is a potent angiogenic factor that induces proliferation, sprouting, migration, and tube formation of endothelial cells. There are three high-affinity tyrosine kinase VEGF receptors (VEGFR-1, Flt-1; VEGFR-2, KDR/Flt-1; and VEGFR-3, Flt-4) on endothelial cells. Several types of non-endothelial cells such as hematopoietic stem cells, melanoma cells, monocytes, osteoblasts, and pancreatic β cells also express VEGF receptors (1).

VEGF receptors were found to be overexpressed in various tumor cells and tumor-associated endothelial cells (3). Inhibition of VEGF receptor function has been shown to inhibit pathological angiogenesis as well as tumor growth and metastasis (4, 5). 123I-VEGF165 has been developed as a single-photon emission computed tomography tracer for imaging solid tumors and angiogenesis in humans (6-8). Yoshimoto et al. (9) compared biodistribution of 125I-VEGF121 and 125I-VEGF165 in an LS180 human colon tumor xenograft model to develop 125I-VEGF121 as an imaging agent to study tumor angiogenesis.

Synthesis

[PubMed]

VEGF121 was labeled with sodium [125I]iodide by electrophilic radioiodination using the chloramine-T method (9). 125I-VEGF121 was purified by gel filtration. This method yielded a specific activity of 0.52–0.74 GBq/nmol (14–20 mCi/nmol). No yield or radiochemical purity values were reported.

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

125I-VEGF121 was stable in mouse serum for up to 4 h at 37°C, and no de-iodination was found (9). Li et al. (6) reported that 123I-VEGF121 (0.001 nM) induced proliferation of human umbilical vein endothelial cells to an extent similar to unlabeled VEGF121, and a high-affinity 125I-VEGF121 binding site (Bmax1 = 5840 ± 20 sites/cell, Kd = 80 ± 13 pM) was found on their cell surfaces.

Animal Studies

Rodents

[PubMed]

Yoshimoto et al. (9) performed biodistribution studies of 125I-VEGF121 and 125I-VEGF165 in nude mice bearing an LS180 human colon tumor. The organs with the highest accumulation of 125I-VEGF121 (in percent of injected dose per gram (% ID/g)) were the uterus (13.76 ± 2.19% ID/g), lung (13.31 ± 2.05% ID/g), kidneys (11.46 ± 0.78% ID/g), tumor (9.12 ± 0.98% ID/g), stomach (8.81 ± 1.87% ID/g), and heart (8.39 ± 0.41% ID/g) at 2 h after injection. 125I-VEGF165 uptake in tumors was one-fold higher than that of 125I-VEGF165 (4.79 ± 1.08% ID/g at 2 h). 125I-VEGF121 exhibited a higher blood radioactivity than 125I-VEGF165 (32.03% versus 5.15% at 2 h). On the other hand, 125I-VEGF165 exhibited a higher accumulation in the stomach (32.79% versus 8.81% at 2 h). 125I-VEGF121 displayed higher tumor/non-tumor ratios in most normal organs than 125I-VEGF165 because 125I-VEGF121 was cleared more rapidly than 125I-VEGF165 from the normal organs. Autoradiographic and immunohistochemical analyses confirmed that the difference in 125I-VEGF121 tumor accumulation correlated with the degree of tumor vascularity. No blocking experiment was performed.

Other Non-Primate Mammals

[PubMed]

No publication is currently available.

Non-Human Primates

[PubMed]

No publication is currently available.

Human Studies

[PubMed]

No publication is currently available.

References

1.
Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev. 2004;25(4):581–611. [PubMed: 15294883]
2.
Cohen T. , Gitay-Goren H. , Sharon R. , Shibuya M. , Halaban R. , Levi B.Z. , Neufeld G. VEGF121, a vascular endothelial growth factor (VEGF) isoform lacking heparin binding ability, requires cell-surface heparan sulfates for efficient binding to the VEGF receptors of human melanoma cells. J Biol Chem. 1995;270(19):11322–6. [PubMed: 7744769]
3.
Soria J.C. , Fayette J. , Armand J.P. Molecular targeting: targeting angiogenesis in solid tumors. Suppl 4Ann Oncol. 2004;15:iv223–7. [PubMed: 15477311]
4.
Ferrara N. Vascular endothelial growth factor as a target for anticancer therapy. Suppl 1Oncologist. 2004;9:2–10. [PubMed: 15178810]
5.
Hicklin D.J. , Ellis L.M. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2005;23(5):1011–27. [PubMed: 15585754]
6.
Li S. , Peck-Radosavljevic M. , Koller E. , Koller F. , Kaserer K. , Kreil A. , Kapiotis S. , Hamwi A. , Weich H.A. , Valent P. , Angelberger P. , Dudczak R. , Virgolini I. Characterization of (123)I-vascular endothelial growth factor-binding sites expressed on human tumour cells: possible implication for tumour scintigraphy. Int J Cancer. 2001;91(6):789–96. [PubMed: 11275981]
7.
Li S. , Peck-Radosavljevic M. , Kienast O. , Preitfellner J. , Hamilton G. , Kurtaran A. , Pirich C. , Angelberger P. , Dudczak R. Imaging gastrointestinal tumours using vascular endothelial growth factor-165 (VEGF165) receptor scintigraphy. Ann Oncol. 2003;14(8):1274–7. [PubMed: 12881392]
8.
Li S. , Peck-Radosavljevic M. , Kienast O. , Preitfellner J. , Havlik E. , Schima W. , Traub-Weidinger T. , Graf S. , Beheshti M. , Schmid M. , Angelberger P. , Dudczak R. Iodine-123-vascular endothelial growth factor-165 (123I-VEGF165). Biodistribution, safety and radiation dosimetry in patients with pancreatic carcinoma. Q J Nucl Med Mol Imaging. 2004;48(3):198–206. [PubMed: 15499293]
9.
Yoshimoto M. , Kinuya S. , Kawashima A. , Nishii R. , Yokoyama K. , Kawai K. Radioiodinated VEGF to image tumor angiogenesis in a LS180 tumor xenograft model. Nucl Med Biol. 2006;33(8):963–9. [PubMed: 17127168]

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