Preparation and comparative evaluation of 99m Tc‐HYNIC‐cNGR and 99m Tc‐HYNIC‐PEG 2 ‐cNGR 99m 99m Tc‐HYNIC‐cNGR and 99m 99m Tc‐HYNIC‐PEG 2 2 ‐cNGR as tumor‐targeting molecular imaging probes

摘要

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‐PEG 2 ‐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‐PEG 2 ‐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‐PEG 2 ‐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 PEG 2 unit, thus posing a challenge for studies with other linkers towards enhanced tumor uptake and retention.