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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

Multispectrally unmixed PA signal intensity as a function of concentration with a line of best fit for each contrast agent.
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f3: Multispectrally unmixed PA signal intensity as a function of concentration with a line of best fit for each contrast agent.

Mentions: In addition, the PA signal for each contrast agent was spectrally unmixed via linear regression. This allows the isolation of the individual contribution of the contrast agent of interest that can be plotted as a function of concentration, which in turn was used to produce a straight line of best fit based on least-squares regression, for each contrast agent. As shown in Figure 3, the line corresponding to ZnPc has the highest gradient, which corresponds to the highest increase in PA signal for an incremental increase in concentration, when compared to the rest. We hereby define this gradient as a form of relative PA quantum yield (φP), a kind of measure of the efficiency of the conversion of light absorption into PA signal. This is analogous to the fluorescence quantum yield (φF), which measures the efficiency of the conversion of light absorption into fluorescence emission. The relative φP of the 5 compounds are computed and listed in Table 1. These are not absolute values, but arbitrary ratios, which reflect the relative PA strength of one compound against that of another. As shown in Table 1, it has also been reported that these photosensitizers have low fluorescence quantum yields (<0.2) but reasonably high singlet oxygen quantum yields (≈0.5). This means that although these photosensitizers can offer high PDT efficacy, they exhibit low fluorescence, which may not be adequate for high contrast diagnostic imaging. However, this limitation can be circumvented by using PA imaging, as shown in this work.


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)

Multispectrally unmixed PA signal intensity as a function of concentration with a line of best fit for each contrast agent.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: Multispectrally unmixed PA signal intensity as a function of concentration with a line of best fit for each contrast agent.
Mentions: In addition, the PA signal for each contrast agent was spectrally unmixed via linear regression. This allows the isolation of the individual contribution of the contrast agent of interest that can be plotted as a function of concentration, which in turn was used to produce a straight line of best fit based on least-squares regression, for each contrast agent. As shown in Figure 3, the line corresponding to ZnPc has the highest gradient, which corresponds to the highest increase in PA signal for an incremental increase in concentration, when compared to the rest. We hereby define this gradient as a form of relative PA quantum yield (φP), a kind of measure of the efficiency of the conversion of light absorption into PA signal. This is analogous to the fluorescence quantum yield (φF), which measures the efficiency of the conversion of light absorption into fluorescence emission. The relative φP of the 5 compounds are computed and listed in Table 1. These are not absolute values, but arbitrary ratios, which reflect the relative PA strength of one compound against that of another. As shown in Table 1, it has also been reported that these photosensitizers have low fluorescence quantum yields (<0.2) but reasonably high singlet oxygen quantum yields (≈0.5). This means that although these photosensitizers can offer high PDT efficacy, they exhibit low fluorescence, which may not be adequate for high contrast diagnostic imaging. However, this limitation can be circumvented by using PA imaging, as shown in this work.

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