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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

(A) Phantom schematic. (B–F) Normalized absorbance (black line) and PA intensity (colored line) as a function of wavelength. The strong correlation between optical absorption and the PA effect is illustrated by the similarity in trend between the two graphs for each contrast agent, with a peak at around 680–700 nm, that tapers downwards towards longer wavelengths.
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f2: (A) Phantom schematic. (B–F) Normalized absorbance (black line) and PA intensity (colored line) as a function of wavelength. The strong correlation between optical absorption and the PA effect is illustrated by the similarity in trend between the two graphs for each contrast agent, with a peak at around 680–700 nm, that tapers downwards towards longer wavelengths.

Mentions: In order to verify the PA activity of these photosensitizers under controlled conditions, we performed phantom measurements for all the contrast agents, in the 680–900 nm wavelength range, each at 5 different concentrations. The phantom is cylindrical with a diameter of 2 cm and contains 2 cylindrical channels in which contrast agents can be placed to measure the PA signal, compared to a control agent (see Figure 2A). During the data acquisition, we recorded data from multiple transverse slices across the channel portion which contains the probe and control, and applied an excitation wavelength scan from 680 to 900 nm with an interval of 10 nm for each transverse slice, and recorded the averaged PA signals from 10 frames for each wavelength and position. After image reconstruction, results showed that all the contrast agents exhibit wavelength-dependent PA activity in phantoms. In addition, there is a similar trend in waveform between absorbance and PA intensity (both normalized) as a function of wavelength for all the contrast agents, with a peak at around 680–700 nm for both absorbance and PA intensity, that tapers downwards towards longer wavelengths. This demonstrates a strong correlation between optical absorption spectra and the PA spectra, which validates our data, as shown in Figure 2(B–F). In PA imaging, the PA intensity induced by optical absorption is proportional to light energy deposition, which is the product of the absorption coefficient and the local light fluence. Thus, the small deviations in trend between absorbance and PA intensities can be attributed to light fluence changes caused by slight variations in laser intensity.


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)

(A) Phantom schematic. (B–F) Normalized absorbance (black line) and PA intensity (colored line) as a function of wavelength. The strong correlation between optical absorption and the PA effect is illustrated by the similarity in trend between the two graphs for each contrast agent, with a peak at around 680–700 nm, that tapers downwards towards longer wavelengths.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: (A) Phantom schematic. (B–F) Normalized absorbance (black line) and PA intensity (colored line) as a function of wavelength. The strong correlation between optical absorption and the PA effect is illustrated by the similarity in trend between the two graphs for each contrast agent, with a peak at around 680–700 nm, that tapers downwards towards longer wavelengths.
Mentions: In order to verify the PA activity of these photosensitizers under controlled conditions, we performed phantom measurements for all the contrast agents, in the 680–900 nm wavelength range, each at 5 different concentrations. The phantom is cylindrical with a diameter of 2 cm and contains 2 cylindrical channels in which contrast agents can be placed to measure the PA signal, compared to a control agent (see Figure 2A). During the data acquisition, we recorded data from multiple transverse slices across the channel portion which contains the probe and control, and applied an excitation wavelength scan from 680 to 900 nm with an interval of 10 nm for each transverse slice, and recorded the averaged PA signals from 10 frames for each wavelength and position. After image reconstruction, results showed that all the contrast agents exhibit wavelength-dependent PA activity in phantoms. In addition, there is a similar trend in waveform between absorbance and PA intensity (both normalized) as a function of wavelength for all the contrast agents, with a peak at around 680–700 nm for both absorbance and PA intensity, that tapers downwards towards longer wavelengths. This demonstrates a strong correlation between optical absorption spectra and the PA spectra, which validates our data, as shown in Figure 2(B–F). In PA imaging, the PA intensity induced by optical absorption is proportional to light energy deposition, which is the product of the absorption coefficient and the local light fluence. Thus, the small deviations in trend between absorbance and PA intensities can be attributed to light fluence changes caused by slight variations in laser intensity.

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