Optical imaging probes are indispensable tools for the visualization of biomarkers of disease without perturbing the biological system. Luminescent lanthanides provide low limits of detection, minimal photobleaching and emit in the first biological window making them ideal for optical imaging; however, as f-f transitions are Laporte-forbidden, organic chromophores absorbing in the 200-300 nm range are necessary for efficient excitation. These excitation wavelengths are not compatible with biological applications. To circumvent this, our group has pioneered in situ excitation of lanthanides with Cherenkov radiation, emitted by positron-emissive radionuclides commonly used in nuclear medicine applications. In situ excitation of lanthanide complexes with Cherenkov radiation energy transfer (CRET) eliminates the need for external high energy, short wavelength excitation. Previously, we have demonstrated that CRET is suitable to excite discrete Tb complexes. Here, we demonstrate our efforts towards the application of Tb and Eu complexes in tandem for multiplexed optical imaging with CRET. With only 10 μCi of 18F, quantities as low as 10 nmol of Eu and as low as 5 nmol Tb complex can be detected (Figure 1). These LOD’s compare favorably with optical chromophores requiring external excitation and motivate us to pursue targeted in vitro and in vivo optical imaging applications. The synthesis and evaluation of bifunctional Tb(III) and Eu(III) complexes targeted to prostate cancer cells expressing the prostate-specific membrane antigen (PSMA) will be presented.

In situ excitation of luminescent lanthanide complexes: Towards enabling in vivo bioimaging

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

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