68Ga Small Peptide Imaging: Comparison of NOTA and PCTA

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• 作者：Cara L. Ferreira ; Donald T. T. Yapp ; Derek Mandel ; Rajanvir K. Gill ; Eszter Boros ; May Q. Wong ; Paul Jurek ; Garry E. Kiefer
• 刊名：Bioconjugate Chemistry
• 出版年：2012
• 出版时间：November 21, 2012
• 年：2012
• 卷：23
• 期：11
• 页码：2239-2246
• 全文大小：341K
• 年卷期：v.23,no.11(November 21, 2012)
• ISSN：1520-4812

文摘

In this study, a bifunctional version of the chelate PCTA was compared to the analogous NOTA derivative for peptide conjugation, ⁶⁸Ga radiolabeling, and small peptide imaging. Both p-SCN-Bn-PCTA and p-SCN-Bn-NOTA were conjugated to cyclo-RGDyK. The resulting conjugates, PCTA-RGD and NOTA-RGD, retained their affinity for the peptide target, the 伪_v尾₃ receptor. Both PCTA-RGD and NOTA-RGD could be radiolabeled with ⁶⁸Ga in >95% radiochemical yield (RCY) at room temperature within 5 min. For PCTA-RGD, higher effective specific activities, up to 55 MBq/nmol, could be achieved in 95% RCY with gentle heating at 40 掳C. The ⁶⁸Ga-radiolabeled conjugates were >90% stable in serum and in the presence of excess apo-transferrin over 4 h; ⁶⁸Ga-PCTA-RGD did have slightly lower stability than ⁶⁸Ga-NOTA-RGD, 93 卤 2% compared to 98 卤 1%, at the 4 h time point. Finally, the tumor and nontarget organ uptake and clearance of ⁶⁸Ga-radiolabeled PCTA-RGD and NOTA-RGD was compared in mice bearing HT-29 colorectal tumor xenografts. Activity cleared quickly from the blood and muscle tissue with >90% and >70% of the initial activity cleared within the first 40 min, respectively. The majority of activity was observed in the kidney, liver, and tumor tissue. The observed tumor uptake was specific with up to 75% of the tumor uptake blocked when the mice were preinjected with 160 nmol (100 渭g) of unlabeled peptide. Uptake observed in the blocked tumors was not significantly different than the background activity observed in muscle tissue. The only significant difference between the two ⁶⁸Ga-radiolabeled bioconjugates in vivo was the kidney uptake. ⁶⁸Ga-radiolabeled PCTA-RGD had significantly lower (p < 0.05) kidney uptake (1.1 卤 0.5%) at 2 h postinjection compared to ⁶⁸Ga-radiolabeled NOTA-RGD (2.7 卤 1.3%). Overall, ⁶⁸Ga-radiolabeled PCTA-RGD and NOTA-RGD performed similarly, but the lower kidney uptake for ⁶⁸Ga-radiolabeled PCTA-RGD may be advantageous in some imaging applications.