Abstract |
pH (low) insertion peptides (pHLIP peptides) target acidic extracellular environments in vivo due to pH-dependent cellular membrane insertion. Two variants (Var3 and Var7) and wild-type (WT) pHLIP peptides have shown promise for in vivo imaging of breast cancer. Two positron emitting radionuclides ((64)Cu and (18)F) were used to label the NOTA- and NO2A-derivatized Var3, Var7, and WT peptides for in vivo biodistribution studies in 4T1 orthotopic tumor-bearing BALB/c mice. All of the constructs were radiolabeled with (64)Cu or [(18)F]-AlF in good yield. The in vivo biodistribution of the 12 constructs in 4T1 orthotopic allografted female BALB/c mice indicated that NO2A-cysVar3, radiolabeled with either (18)F (4T1 uptake; 8.9 ± 1.7%ID/g at 4 h p.i.) or (64)Cu (4T1 uptake; 8.2 ± 0.9%ID/g at 4 h p.i. and 19.2 ± 1.8% ID/g at 24 h p.i.), shows the most promise for clinical translation. Additional studies to investigate other tumor models ( melanoma, prostate, and brain tumor models) indicated the universality of tumor targeting of these tracers. From this study, future clinical translation will focus on (18)F- or (64)Cu-labeled NO2A-cysVar3.
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Authors | Dustin Wayne Demoin, Linden C Wyatt, Kimberly J Edwards, Dalya Abdel-Atti, Mirkka Sarparanta, Jacob Pourat, Valerie A Longo, Sean D Carlin, Donald M Engelman, Oleg A Andreev, Yana K Reshetnyak, Nerissa Viola-Villegas, Jason S Lewis |
Journal | Bioconjugate chemistry
(Bioconjug Chem)
Vol. 27
Issue 9
Pg. 2014-23
(09 21 2016)
ISSN: 1520-4812 [Electronic] United States |
PMID | 27396694
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Copper Radioisotopes
- Fluorine Radioisotopes
- Membrane Proteins
- Radioactive Tracers
- pHLIP protein
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Topics |
- Animals
- Cell Line, Tumor
- Copper Radioisotopes
- Extracellular Space
(chemistry)
- Female
- Fluorine Radioisotopes
- Humans
- Male
- Membrane Proteins
(chemistry, pharmacokinetics)
- Mice
- Mice, Inbred BALB C
- Positron-Emission Tomography
(methods)
- Radioactive Tracers
- Structure-Activity Relationship
- Tissue Distribution
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