Photopharmacological Applications for Cherenkov Radiation Generated by Clinically Used Radionuclides

Krebs, Melanie; Döbber, Alexander; Rodat, Theo; Lützen, Ulf; Zhao, Yi; Zuhayra, Maaz; Peifer, Christian

doi:10.3390/ijms22169010

Cited by 5 publications

(5 citation statements)

References 57 publications

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“…Although our results differ from those of Yoon et al, there are other studies claiming significant effects of CL using Yttrium-90 (high energy beta-emitter similar to Re-188 with an even higher photon yield), Fluorine-18 or other standard radionuclides [ 55 , 57 , 58 , 59 , 60 ].…”

Section: Discussioncontrasting

confidence: 99%

Investigation of Photodynamic Therapy Promoted by Cherenkov Light Activated Photosensitizers—New Aspects and Revelations

Hübinger,

Wetzig,

Runge

et al. 2024

Pharmaceutics

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This work investigates the proposed enhanced efficacy of photodynamic therapy (PDT) by activating photosensitizers (PSs) with Cherenkov light (CL). The approaches of Yoon et al. to test the effect of CL with external radiation were taken up and refined. The results were used to transfer the applied scheme from external radiation therapy to radionuclide therapy in nuclear medicine. Here, the CL for the activation of the PSs (psoralen and trioxsalen) is generated by the ionizing radiation from rhenium-188 (a high-energy beta-emitter, Re-188). In vitro cell survival studies were performed on FaDu, B16 and 4T1 cells. A characterization of the PSs (absorbance measurement and gel electrophoresis) and the CL produced by Re-188 (luminescence measurement) was performed as well as a comparison of clonogenic assays with and without PSs. The methods of Yoon et al. were reproduced with a beam line at our facility to validate their results. In our studies with different concentrations of PS and considering the negative controls without PS, the statements of Yoon et al. regarding the positive effect of CL could not be confirmed. There are slight differences in survival fractions, but they are not significant when considering the differences in the controls. Gel electrophoresis showed a dominance of trioxsalen over psoralen in conclusion of single and double strand breaks in plasmid DNA, suggesting a superiority of trioxsalen as a PS (when irradiated with UVA). In addition, absorption measurements showed that these PSs do not need to be shielded from ambient light during the experiment. An observational test setup for a PDT nuclear medicine approach was found. The CL spectrum of Re-188 was measured. Fluctuating inconclusive results from clonogenic assays were found.

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Section: Discussioncontrasting

confidence: 99%

Investigation of Photodynamic Therapy Promoted by Cherenkov Light Activated Photosensitizers—New Aspects and Revelations

Hübinger,

Wetzig,

Runge

et al. 2024

Pharmaceutics

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“…Even though Y-90 had a photon yield of 47 photons per decay (compared to 35 photons/decay for Re-188), it did not correspond to the high magnitudes. Another recent examination by Krebs et al used the loss of the protective group on the kinase inhibitor AZD5438 as a model to prove the photoactivation [ 6 ]. A clear effect was observed for 419 MBq Y-90.…”

Section: Discussionmentioning

confidence: 99%

“…The small penetration depth of light in the visible and the UV scope, however, limits the applicability of PDT to surface lesions and does not allow for the treatment of solid tumors inside the body. These limitations could be overcome by Cherenkov light (CL), which can be produced by diagnostically or therapeutically used radioisotopes (e.g., Ga-68, Re-188, or Y-90) [ 4 , 5 , 6 ]. CL is already used diagnostically, for example, in visual imaging [ 3 , 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Psoralen as a Photosensitizers for Photodynamic Therapy by Means of In Vitro Cherenkov Light

Hübinger

Runge

Rosenberg

et al. 2022

IJMS

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Possible enhancements of DNA damage with light of different wavelengths and ionizing radiation (Rhenium-188—a high energy beta emitter (Re-188)) on plasmid DNA and FaDu cells via psoralen were investigated. The biophysical experimental setup could also be used to investigate additional DNA damage due to photodynamic effects, resulting from Cherenkov light. Conformational changes of plasmid DNA due to DNA damage were detected and quantified by gel electrophoresis and fluorescent staining. The clonogene survival of the FaDu cells was analyzed with colony formation assays. Dimethyl sulfoxide was chosen as a chemical modulator, and Re-188 was used to evaluate the radiotoxicity and light (UVC: λ = 254 nm and UVA: λ = 366 nm) to determine the phototoxicity. Psoralen did not show chemotoxic effects on the plasmid DNA or FaDu cells. After additional treatment with light (only 366 nm—not seen with 254 nm), a concentration-dependent increase in single strand breaks (SSBs) was visible, resulting in a decrease in the survival fraction due to the photochemical activation of psoralen. Whilst UVC light was phototoxic, UVA light did not conclude in DNA strand breaks. Re-188 showed typical radiotoxic effects with SSBs, double strand breaks, and an overall reduced cell survival for both the plasmid DNA and FaDu cells. While psoralen and UVA light showed an increased toxicity on plasmid DNA and human cancer cells, Re-188, in combination with psoralen, did not provoke additional DNA damage via Cherenkov light.

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“…However, it is not clear whether molecular light compounds can provide adequate energy to switch the Cis‐Trans conformation [163] . Cerenkov luminescence could be a better option for cis‐trans switching and uncaging reactions because a large portion of the spectrum of Cerenkov luminescence is the UV wavelength range [3b,79b,164] …”

Section: Challenges and Limitationsmentioning

confidence: 99%

Molecularly generated light and its biomedical applications

Ran,

2023

Angew Chem Int Ed

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Molecularly generated light, referred to here as “molecular light”, mainly includes bioluminescence, chemiluminescence, and Cerenkov luminescence. Molecular light possesses unique dual features of being both a molecule and a source of light. Its molecular nature enables it to be delivered as molecules to regions deep within the body, overcoming the limitations of natural sunlight and physically generated light sources like lasers and LEDs. Simultaneously, its light properties make it valuable for applications such as imaging, photodynamic therapy, photo‐oxidative therapy, and photobiomodulation. In this review article, we provide an updated overview of the diverse applications of molecular light and discuss the strengths and weaknesses of molecular light across various domains. Lastly, we present forward‐looking perspectives on the potential of molecular light in the realms of molecular imaging, photobiological mechanisms, therapeutic applications, and photobiomodulation. While some of these perspectives may be considered bold and contentious, our intent is to inspire further innovations in the field of molecular light applications.

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Photopharmacological Applications for Cherenkov Radiation Generated by Clinically Used Radionuclides

Cited by 5 publications

References 57 publications

Investigation of Photodynamic Therapy Promoted by Cherenkov Light Activated Photosensitizers—New Aspects and Revelations

Investigation of Photodynamic Therapy Promoted by Cherenkov Light Activated Photosensitizers—New Aspects and Revelations

Psoralen as a Photosensitizers for Photodynamic Therapy by Means of In Vitro Cherenkov Light

Molecularly generated light and its biomedical applications

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