Limits...
Porphyrins as theranostic agents from prehistoric to modern times.

Zhang Y, Lovell JF - Theranostics (2012)

Bottom Line: Long before humans roamed the planet, porphyrins in blood were serving not only as indispensable oxygen carriers, but also as the bright red contrast agent that unmistakably indicates injury sites.Exogenous porphyrins remain in clinical use for photodynamic therapy.Going forward, intrinsic porphyrin biocompatibility and multimodality will keep new applications of this class of molecules at the forefront of theranostic research.

View Article: PubMed Central - PubMed

Affiliation: 1. Department of Chemical and Biological Engineering;

ABSTRACT
Long before humans roamed the planet, porphyrins in blood were serving not only as indispensable oxygen carriers, but also as the bright red contrast agent that unmistakably indicates injury sites. They have proven valuable as whole body imaging modalities have emerged, with endogenous hemoglobin porphyrins being used for new approaches such as functional magnetic resonance imaging and photoacoustic imaging. With the capability for both near infrared fluorescence imaging and phototherapy, porphyrins were the first exogenous agents that were employed with intrinsic multimodal theranostic character. Porphyrins have been used as tumor-specific diagnostic fluorescence imaging agents since 1924, as positron emission agents since 1951, and as magnetic resonance (MR) contrast agents since 1987. Exogenous porphyrins remain in clinical use for photodynamic therapy. Because they can chelate a wide range of metals, exogenous porphyrins have demonstrated potential for use in radiotherapy and multimodal imaging modalities. Going forward, intrinsic porphyrin biocompatibility and multimodality will keep new applications of this class of molecules at the forefront of theranostic research.

No MeSH data available.


Related in: MedlinePlus

Multimodal theranostic capabilities of exogenous porphyrins. a) Human esophageal cancer successfully treated with PDT 36. b) Photothermal image of a xenograft bearing mouse injected with porphysomes and then irradiated by laser for 1 min showing tumor temperature rapidly rising above 60 ºC 44. c) Radiotherapy: Melanoma imaging of 188Re-T3,4 CPP in tumor bearing mice. Scintigraphic images were collected at 8h (a1) and 24 h (a2), showing porphyrin potential in radiotherapy and imaging 85. d) Near infrared fluorescence imaging of porphysome activation in a KB xenograft bearing mouse 44. e) Fluorescence Guided Resection (FGR): the surgical cavity after white light resection of brain tumor in rabbit (top), fluorescence imaging of PpIX showing tumor margins. Additional FGR can improve the accuracy of resection 105. f) Photoacoustic image of rat lymphatics mapped following intradermal injection of porphysomes in rats 44. g) PET imaging showing clear delineation between the tumor and other tissues by PET was obtained at 4, 24 h after intravenous injection of a targeted 64Cu porphyrin 116. h) MR imaging: In the top precontrast T1 weighted image, the infarcted right liver lobe (arrow) was barely detected whereas 24 h after injection of Gadophrin-2 at 0.05 mmol/kg the infarcted liver lobe was strongly enhanced (bottom) 125. Reproduced with permission from the publishers of corresponding references.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3475213&req=5

Figure 2: Multimodal theranostic capabilities of exogenous porphyrins. a) Human esophageal cancer successfully treated with PDT 36. b) Photothermal image of a xenograft bearing mouse injected with porphysomes and then irradiated by laser for 1 min showing tumor temperature rapidly rising above 60 ºC 44. c) Radiotherapy: Melanoma imaging of 188Re-T3,4 CPP in tumor bearing mice. Scintigraphic images were collected at 8h (a1) and 24 h (a2), showing porphyrin potential in radiotherapy and imaging 85. d) Near infrared fluorescence imaging of porphysome activation in a KB xenograft bearing mouse 44. e) Fluorescence Guided Resection (FGR): the surgical cavity after white light resection of brain tumor in rabbit (top), fluorescence imaging of PpIX showing tumor margins. Additional FGR can improve the accuracy of resection 105. f) Photoacoustic image of rat lymphatics mapped following intradermal injection of porphysomes in rats 44. g) PET imaging showing clear delineation between the tumor and other tissues by PET was obtained at 4, 24 h after intravenous injection of a targeted 64Cu porphyrin 116. h) MR imaging: In the top precontrast T1 weighted image, the infarcted right liver lobe (arrow) was barely detected whereas 24 h after injection of Gadophrin-2 at 0.05 mmol/kg the infarcted liver lobe was strongly enhanced (bottom) 125. Reproduced with permission from the publishers of corresponding references.

Mentions: Endogenous porphyrins play a central and historic role in theranostic medicine, but exogenous porphyrins are also of considerable significance. Photodynamic therapy (PDT) is a clinical and minimally invasive method to treat cancers and other diseases. It involves three elements: a photosensitizer, light and oxygen. Porphyrin and porphyrin-related compounds are the most commonly used photosensitizers. After administration and delivery of a photosensitizer to a tumor site and upon light irradiation, it will generate reactive singlet oxygen (1O2), leading to cell death and tumor destruction 30-35. Fig. 2a shows the efficacy of PDT using hexyloxyethyl devinylpyropheophorbide-a (HPPH or Photochlor) in destroying esophageal cancer 36. PDT also has been clinically successful in treating other diseases such as age-related macular degeneration (AMD) and acne 37,38. Singlet oxygen (1O2) has a small diffusion range less than the diameter of a cell, therefore restricting damage only to the treatment site 39. As a variant of PDT, photothermal therapy (PTT) was proposed as another method for cancer treatment using porphyrins at least as early as 1999 40,41. Generally, in the promotion of photothermal sensitized processes, photosensitized species can generate electronic excitation energy upon irradiation, leading to local temperature rises and to the destruction of cancer cells 42, even in the absence of oxygen 43. As shown in Fig 2b, when porphysomes (nanoparticles formed by the conjugation of porphyrin to a phospholipid) were administered to a tumor bearing mouse and irradiated by a 658 nm laser outputting 750 mW with a power density of 1.9 W/cm2 for 1 min, the tumor temperature rapidly increased to 60 ºC while the tumors in control experiment with PBS injected did not increase in temperature beyond 40 ºC 44. Light absorbing species can include metallic nanoparticles (e.g. Au, Ag) 45, cyanine dyes 46, azo-dyes 47, porphyrins 43,48, naphthalocyanines 41 and many others.


Porphyrins as theranostic agents from prehistoric to modern times.

Zhang Y, Lovell JF - Theranostics (2012)

Multimodal theranostic capabilities of exogenous porphyrins. a) Human esophageal cancer successfully treated with PDT 36. b) Photothermal image of a xenograft bearing mouse injected with porphysomes and then irradiated by laser for 1 min showing tumor temperature rapidly rising above 60 ºC 44. c) Radiotherapy: Melanoma imaging of 188Re-T3,4 CPP in tumor bearing mice. Scintigraphic images were collected at 8h (a1) and 24 h (a2), showing porphyrin potential in radiotherapy and imaging 85. d) Near infrared fluorescence imaging of porphysome activation in a KB xenograft bearing mouse 44. e) Fluorescence Guided Resection (FGR): the surgical cavity after white light resection of brain tumor in rabbit (top), fluorescence imaging of PpIX showing tumor margins. Additional FGR can improve the accuracy of resection 105. f) Photoacoustic image of rat lymphatics mapped following intradermal injection of porphysomes in rats 44. g) PET imaging showing clear delineation between the tumor and other tissues by PET was obtained at 4, 24 h after intravenous injection of a targeted 64Cu porphyrin 116. h) MR imaging: In the top precontrast T1 weighted image, the infarcted right liver lobe (arrow) was barely detected whereas 24 h after injection of Gadophrin-2 at 0.05 mmol/kg the infarcted liver lobe was strongly enhanced (bottom) 125. Reproduced with permission from the publishers of corresponding references.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3475213&req=5

Figure 2: Multimodal theranostic capabilities of exogenous porphyrins. a) Human esophageal cancer successfully treated with PDT 36. b) Photothermal image of a xenograft bearing mouse injected with porphysomes and then irradiated by laser for 1 min showing tumor temperature rapidly rising above 60 ºC 44. c) Radiotherapy: Melanoma imaging of 188Re-T3,4 CPP in tumor bearing mice. Scintigraphic images were collected at 8h (a1) and 24 h (a2), showing porphyrin potential in radiotherapy and imaging 85. d) Near infrared fluorescence imaging of porphysome activation in a KB xenograft bearing mouse 44. e) Fluorescence Guided Resection (FGR): the surgical cavity after white light resection of brain tumor in rabbit (top), fluorescence imaging of PpIX showing tumor margins. Additional FGR can improve the accuracy of resection 105. f) Photoacoustic image of rat lymphatics mapped following intradermal injection of porphysomes in rats 44. g) PET imaging showing clear delineation between the tumor and other tissues by PET was obtained at 4, 24 h after intravenous injection of a targeted 64Cu porphyrin 116. h) MR imaging: In the top precontrast T1 weighted image, the infarcted right liver lobe (arrow) was barely detected whereas 24 h after injection of Gadophrin-2 at 0.05 mmol/kg the infarcted liver lobe was strongly enhanced (bottom) 125. Reproduced with permission from the publishers of corresponding references.
Mentions: Endogenous porphyrins play a central and historic role in theranostic medicine, but exogenous porphyrins are also of considerable significance. Photodynamic therapy (PDT) is a clinical and minimally invasive method to treat cancers and other diseases. It involves three elements: a photosensitizer, light and oxygen. Porphyrin and porphyrin-related compounds are the most commonly used photosensitizers. After administration and delivery of a photosensitizer to a tumor site and upon light irradiation, it will generate reactive singlet oxygen (1O2), leading to cell death and tumor destruction 30-35. Fig. 2a shows the efficacy of PDT using hexyloxyethyl devinylpyropheophorbide-a (HPPH or Photochlor) in destroying esophageal cancer 36. PDT also has been clinically successful in treating other diseases such as age-related macular degeneration (AMD) and acne 37,38. Singlet oxygen (1O2) has a small diffusion range less than the diameter of a cell, therefore restricting damage only to the treatment site 39. As a variant of PDT, photothermal therapy (PTT) was proposed as another method for cancer treatment using porphyrins at least as early as 1999 40,41. Generally, in the promotion of photothermal sensitized processes, photosensitized species can generate electronic excitation energy upon irradiation, leading to local temperature rises and to the destruction of cancer cells 42, even in the absence of oxygen 43. As shown in Fig 2b, when porphysomes (nanoparticles formed by the conjugation of porphyrin to a phospholipid) were administered to a tumor bearing mouse and irradiated by a 658 nm laser outputting 750 mW with a power density of 1.9 W/cm2 for 1 min, the tumor temperature rapidly increased to 60 ºC while the tumors in control experiment with PBS injected did not increase in temperature beyond 40 ºC 44. Light absorbing species can include metallic nanoparticles (e.g. Au, Ag) 45, cyanine dyes 46, azo-dyes 47, porphyrins 43,48, naphthalocyanines 41 and many others.

Bottom Line: Long before humans roamed the planet, porphyrins in blood were serving not only as indispensable oxygen carriers, but also as the bright red contrast agent that unmistakably indicates injury sites.Exogenous porphyrins remain in clinical use for photodynamic therapy.Going forward, intrinsic porphyrin biocompatibility and multimodality will keep new applications of this class of molecules at the forefront of theranostic research.

View Article: PubMed Central - PubMed

Affiliation: 1. Department of Chemical and Biological Engineering;

ABSTRACT
Long before humans roamed the planet, porphyrins in blood were serving not only as indispensable oxygen carriers, but also as the bright red contrast agent that unmistakably indicates injury sites. They have proven valuable as whole body imaging modalities have emerged, with endogenous hemoglobin porphyrins being used for new approaches such as functional magnetic resonance imaging and photoacoustic imaging. With the capability for both near infrared fluorescence imaging and phototherapy, porphyrins were the first exogenous agents that were employed with intrinsic multimodal theranostic character. Porphyrins have been used as tumor-specific diagnostic fluorescence imaging agents since 1924, as positron emission agents since 1951, and as magnetic resonance (MR) contrast agents since 1987. Exogenous porphyrins remain in clinical use for photodynamic therapy. Because they can chelate a wide range of metals, exogenous porphyrins have demonstrated potential for use in radiotherapy and multimodal imaging modalities. Going forward, intrinsic porphyrin biocompatibility and multimodality will keep new applications of this class of molecules at the forefront of theranostic research.

No MeSH data available.


Related in: MedlinePlus