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In-vivo photothermal
therapy with palladium(II)octabutoxynaphthalocyanine
Diddens, Heyke1,2,
Fischer, Frank2, DeGroot, Jennifer2
and Pottier, Roy2
Medizinisches Laserzentrum Luebeck, 23562 Luebeck, Germany1
Royal Military College of Canada, Kingston, ON, Canada K7K7B42
Royal Military College of Canada, Kingston, ON, Canada K7K7B43
Royal Military College of Canada, Kingston, ON, Canada K7K7B44
Abstract-
Chromophore-enhanced photothermal therapy (PTT) involves the application
of an an exogenous chromophore in combination with irradiation, using
an appropriate wavelength, exposure duration and sufficient power densities.
In contrast to conventional selective photothermolysis, PTT thus may
allow for highly localized destruction of tissue targets that lack natural
pigmentation via endogenous chromophores. The chromophore palladium(II)octabutoxynaphthalocyanine
(PdNc(OBu)8) accumulates at satisfactory concentrations and with good
selectivity between both tumor and muscle and tumor and skin in tumor-bearing
mice. PdNc(OBu)8 absorbs strongly at 828nm, permitting good penetration
depth of the exciting light, with predominant routes of deexcitation
of the chromophore beeing radiationless thermal processes. Thus, in
an attempt to thermally damage tumor tissue with concurrent sparing
of adjacent normal tissue, the potential of PdNc(OBu)8 for PTT was investigated.
Treatment parameters were based on theoretical calculations including
the photophysical/photochemical properties and pharmacokinetic behavior
of PdNc(OBu)8, and optical properties of tissue in the near-infrared
wavelength range. Using a Balb/c mouse model with subcutaneously implanted
EMT6 adenocarcinoma, 96hrs after intraperitoneal application of PdNc(OBu)8,
the tumor and surrounding tissue were irradiated with a 826nm continuous-wave
diode laser. The laser-induced rise in temperature was monitored by
a thermography camera and the thermal effects on tumor and normal tissue
were evaluated histologically. Our results indicate that after PdNc(OBu)8
administration and tumor irradiation using 5W/cm2 for 100s,
pronounced selective heating of the tumor was achieved in mice, while
in control animals merely an unspecific and marginal overall increase
in temperature over the entire irradiation area was observed. No immediate
effect on overlying skin was detected. Histological evaluation of treated
areas indicated that the PdNc(OBu)8-targeted tumor tissue showed severe
thermal damage while peripheral tissue like skin and muscle remained
largely unaffected. This study shows the potential of creating localized
thermal effects by using PdNc(OBu)8 and continuous-wave light
Keywords: photothermal
therapy, chromophore-enhanced, Pd(II)Octabutoxynaphthalocyanine, in-vivo
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