Abstract
BackgroundPositron emission tomography (PET) allows sensitive, non-invasive analysis of the distribution of radiopharmaceutical tracers labeled with positron (β+)-emitting radionuclides in small animals and humans. Upon β+ decay, the initial velocity of high-energy β+ particles can momentarily exceed the speed of light in tissue, producing Cerenkov radiation that is detectable by optical imaging, but is highly absorbed in living organisms.Principal FindingsTo improve optical imaging of Cerenkov radiation in biological systems, we demonstrate that Cerenkov radiation from decay of the PET isotopes 64Cu and 18F can be spectrally coupled by energy transfer to high Stokes-shift quantum nanoparticles (Qtracker705) to produce highly red-shifted photonic emissions. Efficient energy transfer was not detected with 99mTc, a predominantly γ-emitting isotope. Similar to bioluminescence resonance energy transfer (BRET) and fluorescence resonance energy transfer (FRET), herein we define the Cerenkov radiation energy transfer (CRET) ratio as the normalized quotient of light detected within a spectral window centered on the fluorophore emission divided by light detected within a spectral window of the Cerenkov radiation emission to quantify imaging signals. Optical images of solutions containing Qtracker705 nanoparticles and [18F]FDG showed CRET ratios in vitro as high as 8.8±1.1, while images of mice with subcutaneous pseudotumors impregnated with Qtracker705 following intravenous injection of [18F]FDG showed CRET ratios in vivo as high as 3.5±0.3.ConclusionsQuantitative CRET imaging may afford a variety of novel optical imaging applications and activation strategies for PET radiopharmaceuticals and other isotopes in biomaterials, tissues and live animals.
Highlights
Positron emission tomography (PET) allows sensitive, noninvasive measurement of the distribution of picomolar quantities of radiopharmaceuticals labeled with positron (b+)-emitting radionuclides (e.g., 11C, 18F, 64Cu, 68Ga) in small animals and humans [1]
Quantitative Cerenkov radiation energy transfer (CRET) imaging may afford a variety of novel optical imaging applications and activation strategies for PET radiopharmaceuticals and other isotopes in biomaterials, tissues and live animals
UV/vis emission spectra recorded from phosphate-buffered saline (PBS) containing 70 MBq
Summary
Positron emission tomography (PET) allows sensitive, noninvasive measurement of the distribution of picomolar quantities of radiopharmaceuticals labeled with positron (b+)-emitting radionuclides (e.g., 11C, 18F, 64Cu, 68Ga) in small animals and humans [1]. Because the ultraviolet/blue wavelengths of Cerenkov radiation are highly absorbed in living tissues (by water, hemoglobin, cytochromes, etc.), modest signals and heavily surface-weighted images as recorded by external imaging cameras were produced. To overcome these limitations and provide quantitative optical methods to detect b+ decay in biological tissues, we hypothesized that Cerenkov radiation could be spectrally coupled by energy transfer to high Stokes-shift quantum nanoparticles (Qtracker705) to produce highly red-shifted emission spectra from the decay of PET isotopes compatible with biological imaging. Upon b+ decay, the initial velocity of high-energy b+ particles can momentarily exceed the speed of light in tissue, producing Cerenkov radiation that is detectable by optical imaging, but is highly absorbed in living organisms
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