Effect of the Bifunctional Chelate on the Biodistribution of 99mTc-labeled Cyclic RGD Peptide
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A novel N3S1 chelate, Pro-Lys-Cys (PKC) to cyclic RGD to radiolabel with 99mTc was conjugated in an effort to decrease the high intestinal accumulation observed for 99mTc-labeled PGC-RGD. The target specificity of the resulting PKC-RGD was similar to that of PGC-RGD as determined by a cell binding assay and a competition binding assay. The 99mTc radiolabeling of PKC-RGD resulted in radiochemical yields of 98% under mild conditions at high specific activities. Biodistribution data in normal mice clearly showed a significant decrease in intestinal uptake at 2 h postinjection for the 99mTc-PKC-c (RGDyK) compared to the 99mTc-PGC-c (RGDyK) (from 19.65%ID·g-1 to 7.31%ID·g-1 for the GI tract). The 99mTc-PKC-c (RGDyK) biodistribution was also shown by a higher retention of radioactivity in the whole body, but with kidney accumulation over 8-fold higher than observed with 99mTc-PGC-c (RGDyK) at 2 h (12.62%ID·g-1 for PKC-RGD and 1.54%ID·g-1 for PGC-RGD, respectively). These results show that the biodistribution may be altered especially concerning lipophilicity resulting in renal rather than hepatobiliary excretion. This comparative study made it possible to explore the effects of lipophilicity on the biodistribution of 99mTc-labeled c (RGDyK) through the use of different tripeptide N3S1 chelators. Therefore, 99mTc- PKC-c (RGDyK) may be an attractive alternative for the in vivo imaging of integrin receptors.
Abstract
A novel N3S1 chelate, Pro-Lys-Cys (PKC) to cyclic RGD to radiolabel with 99mTc was conjugated in an effort to decrease the high intestinal accumulation observed for 99mTc-labeled PGC-RGD. The target specificity of the resulting PKC-RGD was similar to that of PGC-RGD as determined by a cell binding assay and a competition binding assay. The 99mTc radiolabeling of PKC-RGD resulted in radiochemical yields of 98% under mild conditions at high specific activities. Biodistribution data in normal mice clearly showed a significant decrease in intestinal uptake at 2 h postinjection for the 99mTc-PKC-c (RGDyK) compared to the 99mTc-PGC-c (RGDyK) (from 19.65%ID·g-1 to 7.31%ID·g-1 for the GI tract). The 99mTc-PKC-c (RGDyK) biodistribution was also shown by a higher retention of radioactivity in the whole body, but with kidney accumulation over 8-fold higher than observed with 99mTc-PGC-c (RGDyK) at 2 h (12.62%ID·g-1 for PKC-RGD and 1.54%ID·g-1 for PGC-RGD, respectively). These results show that the biodistribution may be altered especially concerning lipophilicity resulting in renal rather than hepatobiliary excretion. This comparative study made it possible to explore the effects of lipophilicity on the biodistribution of 99mTc-labeled c (RGDyK) through the use of different tripeptide N3S1 chelators. Therefore, 99mTc- PKC-c (RGDyK) may be an attractive alternative for the in vivo imaging of integrin receptors.
참고문헌 (18)
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