BULLETIN OF THE
Article
Synthesis and Preliminary Evaluation of 68Ga-NOTA-Biphenyl-c(RDGyK)
KOREAN CHEMICAL SOCIETY
According to the representative PET/CT images,
68Ga-NOTA-biphenyl-c(RGDyK) showed the higher tumor
uptake than the reference RGD radioligand (Figure 2).
In the previous study, NOTA-c(RGDyK) had 1.9 nM
of IC50 value. We utilized this RGD peptide as a refer-
ence chelator and performed the cell uptake experiments
in the identical condition. Figure 3 shows the compara-
tive radioactivity uptake patterns. Both radioligands
exhibited comparable liver uptake in the early phase
(30 min), but 68Ga-NOTA-biphenyl-c(RGDyK) showed
a relatively high uptake that was 2–2.6 times (>90 min)
greater than the reference radiopeptide. In the kidney,
68Ga-NOTA-biphenyl-c(RGDyK) exhibited a relatively
low uptake until 45 min, after which its uptake was
1.6–2.2 times (>90 min) higher than that of the refer-
ence. In addition, 68Ga-NOTA-biphenyl-c(RGDyK) dis-
played 1.5–2 times higher muscle uptake than the
reference compound (>75 min) indicating its enhanced
non-specific binding.
Conclusion
68Ga-NOTA-RGD peptides showed enhanced tumor uptake
as well as increased non-specific binding. From these per-
spectives, we demonstrated that adapting biphenyl group
on the RGD peptide has pros and cons.
Acknowledgments. This work was supported by Nuclear
Research and Development Program of the National
Research Foundation of Korea (NRF) grant funded by of
the Korean government (No. 2017M2A2A6A02019904)
and a grant of the Korea Institute of Radiological and Med-
ical Sciences (KIRAMS) funded by the Ministry of Sci-
ence, ICT
& Future Planning, Republic of Korea
(No. 1711045539; 1711045541/50461-2017).
Supporting Information. Additional supporting informa-
tion is available in the online version of this article.
References
Compared with 68Ga-NOTA-c(RGDyK), the tumor
regions are clearly visualized using 68Ga-NOTA-biphenyl-c
(RGDyK). In particular, after 90 min, the tumor uptake of
68Ga-NOTA-c(RGDyK) was faint, whereas the signal for
68Ga-NOTA-biphenyl-c(RGDyK) in the tumor remained
for up to 150 min. These results indicated that incorporat-
ing the biphenyl group enhances the tumor uptake and pro-
longs the retention time. The radioactivities in the heart and
muscle regions showed similar patterns over time to that in
the kidney region.
To compare the specific-to-non-specific binding for both
RGD radioligands, we obtained the tumor-to-muscle ratios
(Figure 4). 68Ga-NOTA-biphenyl-c(RGDyK) showed
higher tumor-to-muscle ratios than those of 68Ga-NOTA-c
(RGDyK) and it reached to equilibrium from 90 min. This
implies that 68Ga-NOTA-biphenyl-c(RGDyK) has kinetic
stability.
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Bull. Korean Chem. Soc. 2017
© 2017 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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