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Image-Based Quantification of Benzoporphyrin Derivative Uptake, Localization, and Photobleaching in 3D Tumor Models, for Optimization of PDT Parameters.

Glidden MD, Celli JP, Massodi I, Rizvi I, Pogue BW, Hasan T - Theranostics (2012)

Bottom Line: While the systematic optimization of these treatment parameters can be complex, it also provides multiple avenues for enhancement of PDT efficacy under diverse treatment conditions, provided that a rational framework is established to quantify the impact of parameter selection upon treatment response.We use this approach to visualize and quantify the uptake, localization, and photobleaching of the PS benzoporphyrin derivative monoacid ring-A (BPD) in a range of treatment conditions with varying uptake times as well as continuous and fractionated light delivery regimens in 3D cultures of AsPC-1 and PANC-1 cells.Quantification of the spatial profile of cell killing within multicellular nodules revealed that these conditions also achieve the highest depth of cytotoxicity along the radial axis of 3D nodules.

View Article: PubMed Central - PubMed

Affiliation: 1. Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA; ; 2. Department of Physics, University of Massachusetts Boston, Boston, MA 02125, USA;

ABSTRACT
Photodynamic therapy (PDT) is a light-based treatment modality in which wavelength specific activation of a photosensitizer (PS) generates cytotoxic response in the irradiated region. PDT response is critically dependent on several parameters including light dose, PS dose, uptake time, fluence rate, and the mode of light delivery. While the systematic optimization of these treatment parameters can be complex, it also provides multiple avenues for enhancement of PDT efficacy under diverse treatment conditions, provided that a rational framework is established to quantify the impact of parameter selection upon treatment response. Here we present a theranostic technique, combining the inherent ability of the PS to serve simultaneously as a therapeutic and imaging agent, with the use of image-based treatment assessment in three dimensional (3D) in vitro tumor models, to comprise a platform to evaluate the impact of PDT parameters on treatment outcomes. We use this approach to visualize and quantify the uptake, localization, and photobleaching of the PS benzoporphyrin derivative monoacid ring-A (BPD) in a range of treatment conditions with varying uptake times as well as continuous and fractionated light delivery regimens in 3D cultures of AsPC-1 and PANC-1 cells. Informed by photobleaching patterns and correlation with cytotoxic response, asymmetric fractionated light delivery at 4 hours BPD uptake was found to be the most effective regimen assessed. Quantification of the spatial profile of cell killing within multicellular nodules revealed that these conditions also achieve the highest depth of cytotoxicity along the radial axis of 3D nodules. The framework introduced here provides a means for systematic assessment of PDT treatment parameters in biologically relevant 3D tumor models with potential for broader application to other systems.

No MeSH data available.


Related in: MedlinePlus

Uptake Dependent Treatment Response for PANC-1 and AsPC-1 Cultures (Continuous Irradiation). Variable treatment response for 5, 10, and 20 J/cm2 irradiance delivered continuously with increasing BPD uptake time for (A) day 12 AsPC-1 and (B) day 10 PANC-1 nodules.
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Figure 3: Uptake Dependent Treatment Response for PANC-1 and AsPC-1 Cultures (Continuous Irradiation). Variable treatment response for 5, 10, and 20 J/cm2 irradiance delivered continuously with increasing BPD uptake time for (A) day 12 AsPC-1 and (B) day 10 PANC-1 nodules.

Mentions: To determine the effect of uptake and localization on treatment response, we conducted continuous irradiation PDT treatments at 1.5 hour, 4 hour, and 24 hour uptake times for both AsPC-1 and PANC-1 cell lines. The 4 hour time point was chosen as the uptake curves in Figure 2 plateau around 4-5 hours while 1.5 hours was chosen as it has been previously studied in 3D cultures 27. Though 24 hour BPD uptake is not practical in in vivo models because of BPD's pharmacokinetics 33, it was nevertheless informative to examine this upper limit in this mechanistic study. Figure 3 shows the results of these experiments. It is readily seen that cytotoxic response is dependent on uptake time for both cell lines. For AsPC-1 cells, at lower light doses (i.e., 5 J/cm2), there is a marked enhancement in killing with increasing uptake. However, killing is either worse or unchanged at higher light doses. PANC-1 cultures show similar behavior, though killing increases going from 1.5 hours to 4 hours with all light doses.


Image-Based Quantification of Benzoporphyrin Derivative Uptake, Localization, and Photobleaching in 3D Tumor Models, for Optimization of PDT Parameters.

Glidden MD, Celli JP, Massodi I, Rizvi I, Pogue BW, Hasan T - Theranostics (2012)

Uptake Dependent Treatment Response for PANC-1 and AsPC-1 Cultures (Continuous Irradiation). Variable treatment response for 5, 10, and 20 J/cm2 irradiance delivered continuously with increasing BPD uptake time for (A) day 12 AsPC-1 and (B) day 10 PANC-1 nodules.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3475211&req=5

Figure 3: Uptake Dependent Treatment Response for PANC-1 and AsPC-1 Cultures (Continuous Irradiation). Variable treatment response for 5, 10, and 20 J/cm2 irradiance delivered continuously with increasing BPD uptake time for (A) day 12 AsPC-1 and (B) day 10 PANC-1 nodules.
Mentions: To determine the effect of uptake and localization on treatment response, we conducted continuous irradiation PDT treatments at 1.5 hour, 4 hour, and 24 hour uptake times for both AsPC-1 and PANC-1 cell lines. The 4 hour time point was chosen as the uptake curves in Figure 2 plateau around 4-5 hours while 1.5 hours was chosen as it has been previously studied in 3D cultures 27. Though 24 hour BPD uptake is not practical in in vivo models because of BPD's pharmacokinetics 33, it was nevertheless informative to examine this upper limit in this mechanistic study. Figure 3 shows the results of these experiments. It is readily seen that cytotoxic response is dependent on uptake time for both cell lines. For AsPC-1 cells, at lower light doses (i.e., 5 J/cm2), there is a marked enhancement in killing with increasing uptake. However, killing is either worse or unchanged at higher light doses. PANC-1 cultures show similar behavior, though killing increases going from 1.5 hours to 4 hours with all light doses.

Bottom Line: While the systematic optimization of these treatment parameters can be complex, it also provides multiple avenues for enhancement of PDT efficacy under diverse treatment conditions, provided that a rational framework is established to quantify the impact of parameter selection upon treatment response.We use this approach to visualize and quantify the uptake, localization, and photobleaching of the PS benzoporphyrin derivative monoacid ring-A (BPD) in a range of treatment conditions with varying uptake times as well as continuous and fractionated light delivery regimens in 3D cultures of AsPC-1 and PANC-1 cells.Quantification of the spatial profile of cell killing within multicellular nodules revealed that these conditions also achieve the highest depth of cytotoxicity along the radial axis of 3D nodules.

View Article: PubMed Central - PubMed

Affiliation: 1. Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA; ; 2. Department of Physics, University of Massachusetts Boston, Boston, MA 02125, USA;

ABSTRACT
Photodynamic therapy (PDT) is a light-based treatment modality in which wavelength specific activation of a photosensitizer (PS) generates cytotoxic response in the irradiated region. PDT response is critically dependent on several parameters including light dose, PS dose, uptake time, fluence rate, and the mode of light delivery. While the systematic optimization of these treatment parameters can be complex, it also provides multiple avenues for enhancement of PDT efficacy under diverse treatment conditions, provided that a rational framework is established to quantify the impact of parameter selection upon treatment response. Here we present a theranostic technique, combining the inherent ability of the PS to serve simultaneously as a therapeutic and imaging agent, with the use of image-based treatment assessment in three dimensional (3D) in vitro tumor models, to comprise a platform to evaluate the impact of PDT parameters on treatment outcomes. We use this approach to visualize and quantify the uptake, localization, and photobleaching of the PS benzoporphyrin derivative monoacid ring-A (BPD) in a range of treatment conditions with varying uptake times as well as continuous and fractionated light delivery regimens in 3D cultures of AsPC-1 and PANC-1 cells. Informed by photobleaching patterns and correlation with cytotoxic response, asymmetric fractionated light delivery at 4 hours BPD uptake was found to be the most effective regimen assessed. Quantification of the spatial profile of cell killing within multicellular nodules revealed that these conditions also achieve the highest depth of cytotoxicity along the radial axis of 3D nodules. The framework introduced here provides a means for systematic assessment of PDT treatment parameters in biologically relevant 3D tumor models with potential for broader application to other systems.

No MeSH data available.


Related in: MedlinePlus