Photonics

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Photonics
Lina Bezdetnaya-Bolotine Associate Professor CRAN
UMR CNRS, Nancy-University, Centre Alexis
Vautrin, FRANCE Head of the Research Unit
of the CAV
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Agenda / content

• Photodynamic therapy (PDT) principle
• Mechanism of photodynamic reactions
• Pre-requisite for effective PDT
• Liposomal formulations of photosensitizers
• Explicit dosimetry
• Implicit dosimetry
• Photobleaching in vivo
• Distribution of pO2 values
• Issues to consider

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1. Photodynamic Therapy principle
Photosensitizer (PS)
Three key-elements
Light
Molecular oxygen
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2. Mechanism of photodynamic reactions
Ps
h?
Type I
Type II
1O2
R. S .-
Ps
O2
R
S
O2
Oxydated Substrate
ROS (H2O2 O2.-, OH.)
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3. Pre-requisites for an effective PDT
Lack of significant selectivity (ratio
tumor/healthy tissues)
Solution targeted photosensitizers (liposomal
forms)
Lack of an adequate dosimetry Solution a
search for the predictive parameters measured
in a non-invasive mode

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4.Photosensitizers in the liposomes
(nanovesicles)
liposomes
photosensitizer
Better selectivity Rapid pharmacokinetics
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5. Photodynamic Dose
Photodynamic Dose (D)
D a x c x F x t
(D, J/m 2)
? constante
C concentration of PS (M)
F fluence rate lumineuse (W/m2) t time (s)
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6. Implicit dosimetry
Photobleaching as a predictive factor for
biological response
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7. Photobleaching in vivo
120
0 (J x cm-2)
100
80
60
Fluorescence inensity (R.U)
40
20
0
600
650
700
750
800
850
Wavelength (nm)
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8. Distribution of pO2 values
Before irradiation
Relative frequency
30
40
5
10
15
20
25
35
Oxygen partial pressure (mmHg)
30 mW/cm2 5-7 J/cm²
Relative frequency
5
10
15
20
25
30
35
40
Oxygen partial pressure (mmHg)
Variations in oxygenation parameters
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9. Issues to consider

• Dynamic changes of the
• concentration of photosesnitizer
• light dose
• oxygen supply

Neccessity to use/develop non-invasive techniques
for PDT monitoring
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10. Issues to consider

• Methods for PDT monitoring of
• blood flow state
• photosensitizer photobleaching
• singlet oxygen production
• optical properties of tissues
• Mathematical modeling for PDT outcome
  prediction

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Thank you

• Lina BOLOTINE
• E-mail l. bolotine_at_nancy.fnclcc.fr
• Tel [phone]
• Fax [phone]
• Web site www.cran.uhp-nancy.fr
• http//www.alexisvautrin.fr/