10.1002/chem.201903390
Chemistry - A European Journal
`COMMUNICATION`
In summary, a modular method for the synthesis of TMIAs
was applied to the synthesis of PSMA-targeted imaging agents
for MRI, PET, and SPECT of prostate cancer. In the approach,
metals utilized for MRI (Gd3+), or placeholders (La3+, Ce3+) for
radioactive metals for PET (Cu2+, Ga3+, In3+, and Y3+) were
chelated to DOTA and placed on the side chains of protected
lysines early in the synthesis to form imaging modules. In one
convergent step, these were coupled directly to a targeting
module consisting of the PSMA-binding urea DCL bonded to an
activated linker.
This modular method provides PSMA-targeted agents for
MRI directly with no further transmetalation or deprotection steps.
By using a placeholder place-holder analogs for PET agents, all
synthetic steps leading to the targeted imaging agent can be
accomplished without the constraints of time and safety aspects
of handling radio-chemicals. Moreover, the agent containing a
placeholder can be transported and stored until a small portion
of it is needed for transmetalation. The very mild acid conditions
for transmetalation are amenable to preparation of PET agents
in a clinical setting.
We thank Mr. Furong Sun, Director of the Mass Spectrometry
Facility, University of Illinois at Urbana-Champaign for the high
resolution mass spectra (HRMS).
We thank Dr. J. Spernyak of the Roswell Park Cancer Center
(RPCC) Translational Imaging Shared Resource (TISR) for MR
imaging support and RPCC support grant P30 CA016056.
Keywords: prostate cancer (PCa) • prostate-specific membrane
antigen (PSMA) • targeted molecular imaging agent (TMIA) •
magnetic resonance imaging (MRI) • positron-emission
tomography (PET)
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Acknowledgements
This research was supported by grant NIH - NCI grants: 1-
R15CA219915-01 (H.S.) and 1-R15CA192148-01 (H.S.) and by
HHS-009-17SF from the S.A.S. Foundation and institutional
support from the NIH grant P30CA06156 (K.L.N).
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We thank the Louis Stokes Alliances for Minority Participation
(LSAMP) at RIT for support for summer research (N.A.), the RIT
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