Abstract |
The tripeptide sequence asparagine-glycine-arginine (NGR) specifically recognizes aminopeptidase N (APN or CD13) receptors highly expressed on tumor cells and vasculature. Thus, NGR peptides can precisely deliver therapeutic and diagnostic compounds to CD13 expressing cancer sites. In this regard, 2 NGR peptide ligands, HYNIC-c(NGR) and HYNIC-PEG2 -c(NGR), were synthesized, radiolabeled with 99m Tc, and evaluated in CD13-positive human fibrosarcoma HT-1080 tumor xenografts. The radiotracers, 99m Tc-HYNIC-c(NGR) and 99m Tc-HYNIC-PEG2 -c(NGR), could be prepared in approximately 95% radiochemical purity and exhibited excellent in vitro and in vivo stability. The radiotracers were hydrophilic in nature with log P values being -2.33 ± 0.05 and -2.61 ± 0.08. The uptake of 2 radiotracers 99m Tc-HYNIC-c(NGR) and 99m Tc-HYNIC-PEG2 -c(NGR) was similar in nude mice bearing human fibrosarcoma HT-1080 tumor xenografts, which was significantly reduced (P < .05) during blocking studies. The 2 radiotracers being hydrophilic cleared rapidly from blood, liver, and intestine and were excreted through renal pathway. The pharmacokinetics of 99m Tc-labeled HYNIC peptide could not be modulated through introduction of PEG2 unit, thus posing a challenge for studies with other linkers towards enhanced tumor uptake and retention.
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Authors | Kusum Vats, Drishty Satpati, Rohit Sharma, Chandan Kumar, Haladhar Dev Sarma, Sharmila Banerjee |
Journal | Journal of labelled compounds & radiopharmaceuticals
(J Labelled Comp Radiopharm)
Vol. 61
Issue 2
Pg. 68-76
(02 2018)
ISSN: 1099-1344 [Electronic] England |
PMID | 29139598
(Publication Type: Journal Article)
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Copyright | Copyright © 2017 John Wiley & Sons, Ltd. |
Chemical References |
- 6-hydrazinopyridine-3-carboxylic acid
- Hydrazines
- NGR peptide
- Nicotinic Acids
- Oligopeptides
- Radiopharmaceuticals
- Polyethylene Glycols
- Technetium
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Topics |
- Animals
- Cell Line, Tumor
- Humans
- Hydrazines
(chemistry)
- Mice
- Mice, Nude
- Neoplasms, Experimental
(diagnostic imaging)
- Nicotinic Acids
(chemistry)
- Oligopeptides
(chemistry)
- Polyethylene Glycols
(chemistry)
- Positron-Emission Tomography
(methods)
- Radiopharmaceuticals
(chemical synthesis, pharmacokinetics)
- Technetium
(chemistry)
- Tissue Distribution
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