Cerenkov Luminescence Imaging of Medical Isotopes

Abstract

The development of novel multimodality imaging agents and techniques represents the current frontier of research in the field of medical imaging science. However, the combination of nuclear tomography with optical techniques has yet to be established. Here, we report the use of the inherent optical emissions from the decay of radiopharmaceuticals for Cerenkov luminescence imaging (CLI) of tumors in vivo and correlate the results with those obtained from concordant immuno-PET studies. Methods: In vitro phantom studies were used to validate the visible light emission observed from a range of radionuclides including the positron emitters 18 F, 64 Cu, 89 Zr, and 124 I; b-emitter 131 I; and a-particle emitter 225 Ac for potential use in CLI. The novel radiolabeled monoclonal antibody 89 Zr-desferrioxamine B [DFO]-J591 for immuno-PET of prostate-specific membrane antigen (PSMA) expression was used to coregister and correlate the CLI signal observed with the immuno-PET images and biodistribution studies. Results: Phantom studies confirmed that Cerenkov radiation can be observed from a range of positron-, b-, and a-emitting radionuclides using standard optical imaging devices. The change in light emission intensity versus time was concordant with radionuclide decay and was also found to correlate linearly with both the activity concentration and the measured PET signal (percentage injected dose per gram). In vivo studies conducted in male severe combined immune deficient mice bearing PSMA-positive, subcutaneous LNCaP tumors demonstrated that tumor-specific uptake of 89 Zr-DFO-J591 could be visualized by both immuno-PET and CLI. Optical and immuno-PET signal intensities were found to increase over time from 24 to 96 h, and biodistribution studies were found to correlate well with both imaging modalities. Conclusion: These studies represent the first, to our knowledge, quantitative assessment of CLI for measuring radiotracer uptake in vivo. Many radionuclides common to both nuclear tomographic imaging and radiotherapy have the potential to be used in CLI. The value of CLI lies in its ability to image radionuclides that do not emit either positrons or g-rays and are, thus, unsuitable for use with current nuclear imaging modalities. Optical imaging of Cerenkov radiation emission shows excellent promise as a potential new imaging modality for the rapid, high-throughput screening of radiopharmaceuticals. In the field of medical imaging science, the concept of multimodality is providing the driving force for the development of the next generation of imaging techniques. The latest hybrid systems such as PET/CT and PET/MRI are transforming the clinical management of cancer patients by consolidating the noninvasive localization and temporal quantification of changes in tissue function and physiology available from PET, with the high-resolution anatomic maps provided by CT or MRI (1,2).In contrast to the immediate clinical impact of nuclear tomographic imaging, optical methods such fluorescencemediated tomography and bioluminescen...

In Vivo Photoactivation Without “Light”: Use of Cherenkov Radiation to Overcome the Penetration Limit of Light

“…Recently, there has been growing interest in the use of photons from Cherenkov radiation for optical imaging [4][5][6][7][8][9][10][11][12] and for excitation of quantum dots and fluorophores in vivo [6,8]. Charged particles such as β + and β − which are generated from radioactive isotope decay can result in visible light with a broad energy range (ca.…”

Harnessing the Power of Radionuclides for Optical Imaging: Cerenkov Luminescence Imaging

“…Statistical analysis showed that both OI and PET displayed good T/N ratios. Examining a range of radionuclides including 18 F, 64 Cu, 89 Zr, 124 I, and 131 I and the a-emitter 225 Ac, Ruggiero et al found that radiance detected by OI and radioactivity detected by PET correlated well in a linear regression model (R 5 0.98 for 89 Zr) (14). They also used a radiolabeled prostate-specific membrane antigen targeting the monoclonal antibody 89 Zrdesferrioxamine B [DFO]-J591 for immuno-PET in LNCaP tumor-bearing mice positive for prostate-specific membrane antigen, and the data correlated well both qualitatively and quantitatively with CLI.…”

“…b 1 -emitters include 11 C, 13 N, 15 O, 18 F, 64 Cu, 68 Ga, and 124 I; Robertson et al used 13 N and 18 F to demonstrate CLI (9). On the other hand, 3 H, 14 C, 32 P, 89 Sr, 90 Y, 131 I, and 177 Lu emit principally high-energy b 2 , and the decay of these emitters is often accompanied by g-rays. Importantly, many b 2 -emitters have already been used for treatment of cancer.…”

“…As previously mentioned, Ruggiero et al developed the 89 Zr-labeled monoclonal antibody 89 Zr-DFO-J591 and demonstrated specific tumor uptake using the inherent CR emitted from this novel radiolabeled immunoconjugate (Supplemental Figs. 2C and 2D; "Cross Validations of CLI" section) (14). As another illustration of the opportunities that CLI makes possible in tumor imaging, Boschi et al studied an experimental mammary cancer model, BB1, and performed dynamic 18 F-FDG uptake measurements in mice carrying these tumors (Supplemental Fig.…”

Cerenkov Luminescence Imaging of Interscapular Brown Adipose Tissue

“…Cerenkov luminescence imaging (CLI), a newly emerged molecular imaging technology [18][19][20][21][22][23][24][25][26] , harnesses the luminescence generated from the + and -decay of radionuclides such as 18 F and 131 I in the medium. The charged particle (such as + and -) polarizes molecules while it travels in the medium [18][19][20] , and luminescence/light is emitted when the polarized molecules relax back to equilibrium.…”