Affiliation:
1. Faculty of Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran
2. Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran
Abstract
Background:
In this study, [64Cu]Cu-NODAGA-RGD-BBN was prepared and its
preclinical assessments were evaluated for PET imaging of GRPR overexpressing tumors.
background:
Among the 64Cu peptide-based radiopharmaceuticals, targeting of GRPRs, somatostatin receptors (SSTRs), and integrins αvβ3, have received the most attention
Methods:
NODAGA-RGD-BBN heterodimer peptide was successfully labeled with cyclotronproduced
copper-64 at optimized conditions. The radiochemical purity of the radiotracer was
checked by HPLC and RTLC methods. The stability of the radiolabeled compound was assessed
in PBS (4°C) and in human blood serum (37°C). Binding affinity and internalization of
[64Cu]Cu-NODAGA-RGD-BBN were studied on PC3, LNCaP, and CHO cell lines. The biodistribution
of the radiotracer was evaluated in normal and tumor-bearing mice.
Results:
[64Cu]Cu-NODAGA-RGD-BBN was prepared with radiochemical purity >99 ± 0.7%
(HPLC/ITLC) and specific activity of 18.5 ± 2.2 TBq/mmol. The radiotracer showed high stability
in PBS (95 ± 1.05%) and in human blood serum (96 ± 1.24%) and, high affinity to the
GRP expressing tumor cells. [64Cu]Cu-NODAGA-RGD-BBN showed hydrophilic (log p =
-1.14) and agonistic nature. The biodistribution and imaging studies demonstrated high uptake
at the tumor site at all intervals post-injection and 3-4 h post-injection can be considered an appropriate
time of imaging.
method:
NODAGA-RGD-BBN heterodimer peptide was successfully labelled with cyclotron-produced copper-64 at optimized conditions. The radiochemical purity of the radiotracer was checked by HPLC and RTLC methods. The stability of the radiolabeled compound was assessed in PBS (4 °C) and in human blood serum (37 °C). Binding affinity and internalization of [64Cu]Cu-NODAGA-RGD-BBN were studied on PC3, LNCaP and CHO cell lines. The biodistribution of the radiotracer was evaluated in normal and tumor-bearing mice.
Conclusion:
The results indicated that [64Cu]Cu-NODAGA-RGD-BBN radiolabeled heterodimer
peptide can be considered as a high-potential agent for PET imaging of GRPRoverexpressing
tumors.
Publisher
Bentham Science Publishers Ltd.