Quantifying the Photochemical Damage Potential of <scp>Contrast‐Enhanced</scp> Fluorescence Imaging Products: Singlet Oxygen Production

Gaitan, Brandon; Frankel, Lucas; Vig, Shruti; Oskoui, Ellen; Adwan, Miriam; Chen, Yu; Elespuru, Rosalie K.; Huang, Huang‐Chiao; Pfefer, T. Joshua

doi:10.1111/php.13638

Cited by 5 publications

(2 citation statements)

References 103 publications

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“…The IR800-IAB2M tracer was considered safe for clinical use since the minibody had already been used in the clinic [15,16] and the fluorophore has been used in numerous clinical applications. Similarly, the photo-induced toxicity of the fluorophore, resulting in the production of singlet oxygen, has been shown to be negligible [17].…”

Section: Introductionmentioning

confidence: 99%

First-in-man study of the PSMA Minibody IR800-IAB2M for molecularly targeted intraoperative fluorescence guidance during radical prostatectomy

Hamdy,

Lamb,

Tullis

et al. 2024

Eur J Nucl Med Mol Imaging

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Purpose Prostate-specific membrane antigen (PSMA) is increasingly used to image prostate cancer in clinical practice. We sought to develop and test a humanised PSMA minibody IAB2M conjugated to the fluorophore IRDye 800CW-NHS ester in men undergoing robot-assisted laparoscopic radical prostatectomy (RARP) to image prostate cancer cells during surgery. Methods The minibody was evaluated pre-clinically using PSMA positive/negative xenograft models, following which 23 men undergoing RARP between 2018 and 2020 received between 2.5 mg and 20 mg of IR800-IAB2M intravenously, at intervals between 24 h and 17 days prior to surgery. At every step of the procedure, the prostate, pelvic lymph node chains and extra-prostatic surrounding tissue were imaged with a dual Near-infrared (NIR) and white light optical platform for fluorescence in vivo and ex vivo. Histopathological evaluation of intraoperative and postoperative microscopic fluorescence imaging was undertaken for verification. Results Twenty-three patients were evaluated to optimise both the dose of the reagent and the interval between injection and surgery and secure the best possible specificity of fluorescence images. Six cases are presented in detail as exemplars. Overall sensitivity and specificity in detecting non-lymph-node extra-prostatic cancer tissue were 100% and 65%, and 64% and 64% respectively for lymph node positivity. There were no side-effects associated with administration of the reagent. Conclusion Intraoperative imaging of prostate cancer tissue is feasible and safe using IR800-IAB2M. Further evaluation is underway to assess the benefit of using the technique in improving completion of surgical excision during RARP. Registration ISCRCTN10046036: https://www.isrctn.com/ISRCTN10046036.

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Section: Introductionmentioning

confidence: 99%

First-in-man study of the PSMA Minibody IR800-IAB2M for molecularly targeted intraoperative fluorescence guidance during radical prostatectomy

Hamdy,

Lamb,

Tullis

et al. 2024

Eur J Nucl Med Mol Imaging

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“…In addition, the singlet oxygen atom also plays an important role in photochemistry. [23][24][25] In this study, we performed MD simulations combined with density functional theory (DFT) to study the reaction mecha-nisms for oxygen atom and chlorine ion in NaCl solutions. Considering the ground and first excited states of the oxygen atom, we examined four bulk systems, O( 3 P)-NaCl-63H 2 O, O( 1 D)-NaCl-63H 2 O, O( 3 P)-4NaCl-63H 2 O, and O( 1 D)-4NaCl-63H 2 O. MD simulations were performed on 256 trajectories that underwent sixty-four initial configurations of every system.…”

Section: Introductionmentioning

confidence: 99%

Elucidation of Molecular‐level Mechanisms of Oxygen Atom Reactions with Chlorine Ion in NaCl Solutions using Molecular Dynamics Simulations Combined with Density Functional Theory

Jirásek

Lukeš

2023

ChemistrySelect

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Molecular dynamics simulations combined with density functional theory were performed to investigate the reaction mechanisms for oxygen atom and chlorine ion in NaCl solutions. Considering the ground and first excited states of the oxygen atom, four bulk systems, O(3P)‐NaCl‐63H2O, O(1D)‐NaCl‐63H2O, O(3P)‐4NaCl‐63H2O, and O(1D)‐4NaCl‐63H2O were studied. The main reaction pathway depended on the concentration of the aqueous electrolyte solution. For a dilute solution with a 1 : 64 ratio of NaCl to H2O, the singlet oxygen atom first attached a water molecule to produce a neutral OH radical, and then the OH radical and chlorine ion approach each other to form an intermediate structure [Cl…OH]−. Synchronously, the intermediate transferred charge to the solvated OH radical by accessing the hydrogen bond network. Finally, neutral HOCl and OH− ions were formed. For a dense solution with a 4 : 64 ratio of NaCl to H2O, a singlet oxygen atom was directly combined with Cl− to produce ClO− via an oxygen transfer reaction. The subsequent ab‐initio energy computations indicated the most probable mechanism, where the O atom directly combines with Cl− ion to OCl−. This study provides insights into the fundamental mechanisms of the behavior of dissolved oxygen radicals in aqueous electrolyte solutions.

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Light‐activatable minimally invasive ethyl cellulose ethanol ablation: Biodistribution and potential applications

Yang,

Ma,

Quinlan

et al. 2024

Bioengineering & Transla Med

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While surgical resection is a mainstay of cancer treatment, many tumors are unresectable due to stage, location, or comorbidities. Ablative therapies, which cause local destruction of tumors, are effective alternatives to surgical excision in several settings. Ethanol ablation is one such ablative treatment modality in which ethanol is directly injected into tumor nodules. Ethanol, however, tends to leak out of the tumor and into adjacent tissue structures, and its biodistribution is difficult to monitor in vivo. To address these challenges, this study presents a cutting‐edge technology known as Light‐Activatable Sustained‐Exposure Ethanol Injection Technology (LASEIT). LASEIT comprises a three‐part formulation: (1) ethanol, (2) benzoporphyrin derivative, which enables fluorescence‐based tracking of drug distribution and the potential application of photodynamic therapy, and (3) ethyl cellulose, which forms a gel upon injection into tissue to facilitate drug retention. In vitro drug release studies showed that ethyl cellulose slowed the rate of release in LASEIT by 7×. Injections in liver tissues demonstrated a 6× improvement in volume distribution when using LASEIT compared to controls. In vivo experiments in a mouse pancreatic cancer xenograft model showed LASEIT exhibited significantly stronger average radiant efficiency than controls and persisted in tumors for up to 7 days compared to controls, which only persisted for less than 24 h. In summary, this study introduced LASEIT as a novel technology that enabled real‐time fluorescence monitoring of drug distribution both ex vivo and in vivo. Further research exploring the efficacy of LASEIT is strongly warranted.

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Quantifying the Photochemical Damage Potential of Contrast‐Enhanced Fluorescence Imaging Products: Singlet Oxygen Production

Cited by 5 publications

References 103 publications

First-in-man study of the PSMA Minibody IR800-IAB2M for molecularly targeted intraoperative fluorescence guidance during radical prostatectomy

First-in-man study of the PSMA Minibody IR800-IAB2M for molecularly targeted intraoperative fluorescence guidance during radical prostatectomy

Elucidation of Molecular‐level Mechanisms of Oxygen Atom Reactions with Chlorine Ion in NaCl Solutions using Molecular Dynamics Simulations Combined with Density Functional Theory

Light‐activatable minimally invasive ethyl cellulose ethanol ablation: Biodistribution and potential applications

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