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Multifunctional photosensitizer-based contrast agents for photoacoustic imaging.

Ho CJ, Balasundaram G, Driessen W, McLaren R, Wong CL, Dinish US, Attia AB, Ntziachristos V, Olivo M - Sci Rep (2014)

Bottom Line: Photoacoustic imaging is a novel hybrid imaging modality combining the high spatial resolution of optical imaging with the high penetration depth of ultrasound imaging.Photoacoustic imaging of photosensitizers exhibits advantages over fluorescence imaging, which is prone to photobleaching and autofluorescence interference.In this work, we examined the photoacoustic activity of 5 photosensitizers: zinc phthalocyanine, protoporphyrin IX, 2,4-bis [4-(N,N-dibenzylamino)-2,6-dihydroxyphenyl] squaraine, chlorin e6 and methylene blue in phantoms, among which zinc phthalocyanine showed the highest photoacoustic activity.

View Article: PubMed Central - PubMed

Affiliation: Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore.

ABSTRACT
Photoacoustic imaging is a novel hybrid imaging modality combining the high spatial resolution of optical imaging with the high penetration depth of ultrasound imaging. Here, for the first time, we evaluate the efficacy of various photosensitizers that are widely used as photodynamic therapeutic (PDT) agents as photoacoustic contrast agents. Photoacoustic imaging of photosensitizers exhibits advantages over fluorescence imaging, which is prone to photobleaching and autofluorescence interference. In this work, we examined the photoacoustic activity of 5 photosensitizers: zinc phthalocyanine, protoporphyrin IX, 2,4-bis [4-(N,N-dibenzylamino)-2,6-dihydroxyphenyl] squaraine, chlorin e6 and methylene blue in phantoms, among which zinc phthalocyanine showed the highest photoacoustic activity. Subsequently, we evaluated its tumor localization efficiency and biodistribution at multiple time points in a murine model using photoacoustic imaging. We observed that the probe localized at the tumor within 10 minutes post injection, reaching peak accumulation around 1 hour and was cleared within 24 hours, thus, demonstrating the potential of photosensitizers as photoacoustic imaging contrast agents in vivo. This means that the known advantages of photosensitizers such as preferential tumor uptake and PDT efficacy can be combined with photoacoustic imaging capabilities to achieve longitudinal monitoring of cancer progression and therapy in vivo.

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Related in: MedlinePlus

In vivo non-background-corrected MIP images of transverse slices through mouse at various time points postinjection, demonstrating strong probe MSOT signals within the liver, spleen, kidneys, intestines and tumor site.There is a gradual decrease in the tumor MSOT signal over time, which in turn implies probe clearance within a day.
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f5: In vivo non-background-corrected MIP images of transverse slices through mouse at various time points postinjection, demonstrating strong probe MSOT signals within the liver, spleen, kidneys, intestines and tumor site.There is a gradual decrease in the tumor MSOT signal over time, which in turn implies probe clearance within a day.

Mentions: Based on the prioritization of the different photosensitizers for MSOT imaging by phantom analysis, we next evaluated ZnPc in vivo, since it was found to have the strongest PA signal in phantoms. In essence, we injected ZnPc intravenously into mice bearing subcutaneous tumor and monitored the probe uptake over time in the liver, spleen, kidneys, intestines and tumor using PA imaging. We scanned a volume ROI consisting of transverse slices spanning from the liver to the lower abdomen and constructed maximum intensity projections (MIPs) based on these slices for image analysis. A strong in vivo MSOT signal of ZnPc was detected in the reticuloendothelial system (liver, spleen), intestines and tumor site within the first hour after injection, with peak accumulation at the 1-hour time point, as shown in the background-corrected images in Figure 4. In addition, the non-background-corrected images in Figure 5 and Figure 6A shows that this signal gradually drops in intensity beyond 1 hour up to a day, suggesting probe clearance within a day. This allows for the rapid evaluation of PDT agent delivery after administration and can aid in optimizing PDT and not full form time point planning. Apart from monitoring the accumulation in tumor, the whole-body biodistribution of compounds can be visualized and quantified simultaneously by MSOT, which can aid in the elucidation of clearance pathways and choosing of optimal dosing strategies. We hypothesize that ZnPc is most likely cleared through the hepatobiliary system, because high concentrations are found in the liver and intestines up to the 3-hour time point, whereas renal signal is much weaker in comparison, as shown in Figure 5 and Figure 6A. In addition, Figure 6B also shows a peak tumor-to-muscle ratio of the MSOT signal at the 1-hour time point, making this time point ideal for PDT illumination and subsequent monitoring via MSOT imaging. Thus, in summary, the strong MSOT signals from ZnPc observed in the tumor region at the 1-hour time point suggests that MSOT imaging, combined with PDT, offers a novel theranostic approach with high translational potential.


Multifunctional photosensitizer-based contrast agents for photoacoustic imaging.

Ho CJ, Balasundaram G, Driessen W, McLaren R, Wong CL, Dinish US, Attia AB, Ntziachristos V, Olivo M - Sci Rep (2014)

In vivo non-background-corrected MIP images of transverse slices through mouse at various time points postinjection, demonstrating strong probe MSOT signals within the liver, spleen, kidneys, intestines and tumor site.There is a gradual decrease in the tumor MSOT signal over time, which in turn implies probe clearance within a day.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061552&req=5

f5: In vivo non-background-corrected MIP images of transverse slices through mouse at various time points postinjection, demonstrating strong probe MSOT signals within the liver, spleen, kidneys, intestines and tumor site.There is a gradual decrease in the tumor MSOT signal over time, which in turn implies probe clearance within a day.
Mentions: Based on the prioritization of the different photosensitizers for MSOT imaging by phantom analysis, we next evaluated ZnPc in vivo, since it was found to have the strongest PA signal in phantoms. In essence, we injected ZnPc intravenously into mice bearing subcutaneous tumor and monitored the probe uptake over time in the liver, spleen, kidneys, intestines and tumor using PA imaging. We scanned a volume ROI consisting of transverse slices spanning from the liver to the lower abdomen and constructed maximum intensity projections (MIPs) based on these slices for image analysis. A strong in vivo MSOT signal of ZnPc was detected in the reticuloendothelial system (liver, spleen), intestines and tumor site within the first hour after injection, with peak accumulation at the 1-hour time point, as shown in the background-corrected images in Figure 4. In addition, the non-background-corrected images in Figure 5 and Figure 6A shows that this signal gradually drops in intensity beyond 1 hour up to a day, suggesting probe clearance within a day. This allows for the rapid evaluation of PDT agent delivery after administration and can aid in optimizing PDT and not full form time point planning. Apart from monitoring the accumulation in tumor, the whole-body biodistribution of compounds can be visualized and quantified simultaneously by MSOT, which can aid in the elucidation of clearance pathways and choosing of optimal dosing strategies. We hypothesize that ZnPc is most likely cleared through the hepatobiliary system, because high concentrations are found in the liver and intestines up to the 3-hour time point, whereas renal signal is much weaker in comparison, as shown in Figure 5 and Figure 6A. In addition, Figure 6B also shows a peak tumor-to-muscle ratio of the MSOT signal at the 1-hour time point, making this time point ideal for PDT illumination and subsequent monitoring via MSOT imaging. Thus, in summary, the strong MSOT signals from ZnPc observed in the tumor region at the 1-hour time point suggests that MSOT imaging, combined with PDT, offers a novel theranostic approach with high translational potential.

Bottom Line: Photoacoustic imaging is a novel hybrid imaging modality combining the high spatial resolution of optical imaging with the high penetration depth of ultrasound imaging.Photoacoustic imaging of photosensitizers exhibits advantages over fluorescence imaging, which is prone to photobleaching and autofluorescence interference.In this work, we examined the photoacoustic activity of 5 photosensitizers: zinc phthalocyanine, protoporphyrin IX, 2,4-bis [4-(N,N-dibenzylamino)-2,6-dihydroxyphenyl] squaraine, chlorin e6 and methylene blue in phantoms, among which zinc phthalocyanine showed the highest photoacoustic activity.

View Article: PubMed Central - PubMed

Affiliation: Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore.

ABSTRACT
Photoacoustic imaging is a novel hybrid imaging modality combining the high spatial resolution of optical imaging with the high penetration depth of ultrasound imaging. Here, for the first time, we evaluate the efficacy of various photosensitizers that are widely used as photodynamic therapeutic (PDT) agents as photoacoustic contrast agents. Photoacoustic imaging of photosensitizers exhibits advantages over fluorescence imaging, which is prone to photobleaching and autofluorescence interference. In this work, we examined the photoacoustic activity of 5 photosensitizers: zinc phthalocyanine, protoporphyrin IX, 2,4-bis [4-(N,N-dibenzylamino)-2,6-dihydroxyphenyl] squaraine, chlorin e6 and methylene blue in phantoms, among which zinc phthalocyanine showed the highest photoacoustic activity. Subsequently, we evaluated its tumor localization efficiency and biodistribution at multiple time points in a murine model using photoacoustic imaging. We observed that the probe localized at the tumor within 10 minutes post injection, reaching peak accumulation around 1 hour and was cleared within 24 hours, thus, demonstrating the potential of photosensitizers as photoacoustic imaging contrast agents in vivo. This means that the known advantages of photosensitizers such as preferential tumor uptake and PDT efficacy can be combined with photoacoustic imaging capabilities to achieve longitudinal monitoring of cancer progression and therapy in vivo.

Show MeSH
Related in: MedlinePlus