Numerous peptides that bind to a given target have been selected by phage display technology. However, some peptides isolated to date do not bind with high affinity to tumor or organ sites, even peptides were selected in vivo. Therefore, the biodistribution of 99mTc-labeled filamentous phage peptide library via MAG3 (mercaptoacetyltriglycine) were investigated to gain a better understanding of phage circulation in vivo. The experimental results showed that the liver and spleen were the organs of the greatest accumulation, while heart, muscle, pancreas and brain retained less radioactivity. In opposite to other tissues and organs, the radioactivity in stomach, intestine and bone gradually went up with time. The clearance of 99mTc-labeled phage in blood was very fast from 5 min to 30 min and then slowed down. When phage in vivo circulated at enough long period of time, some phage particles could extravasate in some organs or tissues and internalized there. In conclusion, the circulation time of phage in vivo should be experimentally determined beforehand according to the targeted organs and the specific location of target peptides in order to panning a peptide with high specificity and affinity to that target.

Objective To evaluate the hypoxia selectivity of 99 Tcm O?labeld MAG3?nitroimidazole complexes with different spacers. Methods Four kinds of 99 Tcm O?labeled MAG3?2?nitroimidazole hypoxia imaging agents with different spacers were synthesized and radiolabeled. The stability and lipid solubility of BzMAG3?2NIEA(1), BzMAG3?2NIPA(2), BzMAG3?2NIHA(3) and BzMAG3?2NIUA(4) were measured. The uptake was investigated by biodistribution experiment using S180?bearing mice. Two?sample t test was used for statistical analysis. Results All 4 99 Tcm O?MAG3 complexes were stable and negatively charged, showing an increasing trend in fat solubility with the increase of spacer length. In biodistribution study, tumor uptake of 99TcmO?1 and 99TcmO?2 with medium? and short?carbon chain were (0.67±0.18) and (0?65±0.18) %ID/g 2 h post injection, which were (0.19±0.03) and (0.39±0.05) %ID/g for 99TcmO?3 and 99TcmO?4 with long?carbon chain (t=2.78-5.88, all P<0.05). Conclusion Molecular structure of spacers has a significant effect on the physicochemical properties and tumor targeting of 99 Tcm O?labeled MAG3?2?nitroimidazole hypoxia imaging agents, such that the medium?and short?carbon chain spacers show the best hypoxia?selective property.