A Comparison of Singlet Oxygen Explicit Dosimetry (SOED) and Singlet Oxygen Luminescence Dosimetry (SOLD) for Photofrin-Mediated Photodynamic Therapy

Our plain-English summary of A Comparison of Singlet Oxygen Explicit Dosimetry (SOED) and Singlet Oxygen Luminescence Dosimetry (SOLD) for Photofrin-Mediated Photodynamic Therapy, by M.M. Kim, R. Penjweini, N.R. Gemmell, et al (Cancers, 2016).

The study

• Authors: M.M. Kim, R. Penjweini, N.R. Gemmell, I. Veilleux, A. McCarthy, G.S. Buller, R.H. Hadfield, B.C. Wilson, T.C. Zhu
• Journal: Cancers
• Published: 2016;8(12)
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Accurate photodynamic therapy (PDT) dosimetry is critical for the use of PDT in the treatment of malignant and nonmalignant localized diseases. A singlet oxygen explicit dosimetry (SOED) model has been developed for in vivo purposes. It involves the measurement of the key components in PDT-light fluence (rate), photosensitizer concentration, and ground-state oxygen concentration ([³O₂])-to calculate the amount of reacted singlet oxygen ([¹O₂]rx), the main cytotoxic component in type II PDT. Experiments were performed in phantoms with the photosensitizer Photofrin and in solution using phosphorescence-based singlet oxygen luminescence dosimetry (SOLD) to validate the SOED model. Oxygen concentration and photosensitizer photobleaching versus time were measured during PDT, along with direct SOLD measurements of singlet oxygen and triplet state lifetime (τΔ and τt), for various photosensitizer concentrations to determine necessary photophysical parameters. SOLD-determined cumulative [¹O₂]rx was compared to SOED-calculated [¹O₂]rx for various photosensitizer concentrations to show a clear correlation between the two methods. This illustrates that explicit dosimetry can be used when phosphorescence-based dosimetry is not feasible. Using SOED modeling, we have also shown evidence that SOLD-measured [¹O₂]rx using a 523 nm pulsed laser can be used to correlate to singlet oxygen generated by a 630 nm laser during a clinical malignant pleural mesothelioma (MPM) PDT protocol by using a conversion formula.

In plain English

This laboratory and modeling study compared two ways of estimating singlet oxygen, which the authors call the main cell-killing agent in Photofrin photodynamic therapy (PDT). Singlet oxygen explicit dosimetry (SOED) calculates it from measured light, drug and oxygen; luminescence dosimetry (SOLD) detects the near-infrared light it emits. In tissue-simulating liquid phantoms, SOED calculations agreed with oxygen and drug levels measured at the surface. The two methods were compared directly in Photofrin-methanol solutions lit at 523 nm. There, cumulative SOLD counts and SOED-calculated reacted singlet oxygen tracked closely (R2 = 0.98), though the authors did not know why the fitted line had an intercept. Using optical properties measured in malignant pleural mesothelioma patients, SOED calculations gave a formula linking reacted singlet oxygen at 523 nm (the SOLD laser wavelength) to 630 nm (the clinical wavelength). Applying it to patients' SOLD signals would also need a correction for tissue absorption and scattering of the luminescence; the authors said this was beyond this paper's scope. The authors concluded that the methods correlate well and that SOED must be validated for each drug and clinical setting. The study did not examine asbestos.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory experiments in solutions and tissue-simulating phantoms, combined with computer modeling (Monte Carlo light simulations) that used tissue optical properties measured in patients
• Who was studied: Photofrin solutions in methanol, used for the direct SOED and SOLD comparison. Intralipid tissue-simulating liquid phantoms, used to check SOED against measured oxygen and Photofrin levels. Separately, optical properties were measured at multiple tissue sites in several patients undergoing pleural PDT for malignant pleural mesothelioma under an IRB-approved Photofrin-PDT clinical protocol at the University of Pennsylvania. The number of patients is not given.
• Exposure: Photofrin-mediated photodynamic therapy light. A 523 nm pulsed laser was used for SOLD measurements, and continuous 630 nm laser light (the clinical treatment wavelength) was used in the phantoms. No asbestos exposure was studied.
• Main results:
  • In Photofrin phantoms, the values obtained were delta = 25 plus or minus 4.3 µM and sigma = (6.6 plus or minus 7) × 10^-5 per µM.
  • SOED calculations agreed with oxygen and Photofrin concentrations measured over time at the surface of the Intralipid phantom.
  • SOLD lifetime measurements in Photofrin and methanol solutions with sodium azide gave k7 = 235 per µM per second.
  • In Photofrin solutions (Photofrin dissolved in methanol, no scatterer added), cumulative SOLD counts and SOED-calculated reacted singlet oxygen tracked each other very well (R2 = 0.98). A linear fit without an intercept reduced the correlation (R2 = 0.86).
  • Using optical properties measured in malignant pleural mesothelioma patients, light penetration was much deeper at 630 nm than at 523 nm.
  • Based on SOED calculations using patient optical properties at the two wavelengths, the authors established a formula (Equations 11 to 13) for converting cumulative SOLD signal measured at 523 nm to the corresponding reacted singlet oxygen at 630 nm. Applying it to SOLD signals from patients would also require a tissue optical properties correction for the luminescence, which the paper did not develop.
• The authors' conclusion: The authors concluded that, with suitable correction for tissue optical properties at the two wavelengths, there is excellent correlation between the direct (SOLD) and indirect (SOED) estimates of singlet oxygen generated during PDT. They said this validation supports the use of SOED in clinical dosimetry.
• Limitations the authors state:
  • The reason for the intercept in the SOLD/SOED relationship is not known.
  • Using SOLD signals from patients would require a tissue optical properties correction factor for the luminescence. The authors state this is beyond the scope of the paper.
  • SOED relies on simplifying assumptions that SOLD does not need.
  • SOED must be validated for each photosensitizer and set of clinical conditions.
  • Only a 523 nm pulsed laser was available for SOLD, so it does not sample tissue at the same depth as the 630 nm clinical treatment light.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma.

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