Localized thermal tumor destruction using dye-enhanced photothermal tumor therapy.

BACKGROUND AND OBJECTIVE: In an attempt to develop a new therapeutic approach for highly localized thermal destruction of tissue targets that lack natural pigmentation, the potential of in-vivo dye-enhanced photothermal therapy (PTT) was investigated. PTT involves the application of an exogenous absorber, which accumulates in metabolically active tissues, followed by non-invasive light irradiation, using appropriate wavelengths, exposure durations, and irradiances. The chromophore used, palladium(II) octabutoxynaphthalocyanine (PdNc(OBu)8 ), strongly absorbs in the near infrared wavelength range which thus permits good penetration depth of the exciting light. The predominant de-excitation routes of the chromophore are radiationless thermal processes. MATERIALS AND METHODS: Using a BALB/c mouse model with a subcutaneously implanted syngeneic EMT6 adenocarcinoma, 96-100 hours after intraperitoneal application of PdNc(OBu)8 , tumor, and surrounding tissue were irradiated with a 830 nm continuous wave diode laser applying 30 Wcm(-2) for 10-20 seconds. Treatment parameters were based on theoretical calculations. RESULTS: Histological evaluation of thermal effects on tumor and normal tissue showed that after PdNc(OBu)8 -enhanced photothermal treatment, highly localized and selective thermal damage of the tumors was achieved. The necrotic tumor area was invaded by inflammatory cells, including neutrophils, macrophages, mast cells, and lymphocytes, thus reflecting a prominent host immune response. In tumors treated with PTT for 15 or 20 seconds, respectively, only few surviving tumor cells were detected underneath the epidermis. Adjacent peripheral normal tissue including skin and muscle remained completely unaffected. CONCLUSION: This study highlights the potential of achieving irreversible thermal tissue damage closely localized to the target tissue when PdNc(OBu)8 is used in combination with continuous-wave light.

Determination of the in vivo pharmacokinetics of palladium-bacteriopheophorbide (WST09) in EMT6 tumour-bearing Balb/c mice using graphite furnace atomic absorption spectroscopy.

Palladium-bacteriopheophorbide (WST09), a novel bacteriochlorophyll derivative, is currently being investigated for use as a photodynamic therapy (PDT) drug due to its strong absorption in the near-infrared region and its ability to efficiently generate singlet oxygen when irradiated. In this study, we determined the pharmacokinetics and tissue distribution of WST09 in female EMT6 tumour-bearing Balb/c mice in order to determine if selective accumulation of this drug occurs in tumour tissue. A total of 41 mice were administered WST09 by bolus injection into the tail vein at a dose level of 5.0 +/- 0.8 mg kg(-1). Three to six mice were sacrificed at each of 0.08, 0.25, 0.5, 1.0, 3.0, 6.0, 9.0, 12, 24, 48, 72, and 96 h post injection, and an additional three control mice were sacrificed without having been administered WST09. Terminal blood samples as well as liver, skin, muscle, kidney and tumour samples were obtained from each mouse and analyzed for palladium content (from WST09) using graphite furnace atomic absorption spectroscopy (GFAAS). The representative concentration of WST09 in the plasma and tissues was then calculated. Biphasic kinetics were observed in the plasma, kidney, and liver with clearance from each of these tissues being relatively rapid. Skin, muscle and tumour did not show any significant accumulation at all time points investigated. No selective drug accumulation was seen in the tumour and normal tissues, relative to plasma. Thus the results of this study indicate that vascular targeting resulting from WST09 in the circulation, as opposed to selective WST09 accumulation in tumour tissues, may be responsible for PDT effects in tumours that have been observed in other WST09 studies.

In-vivo investigations on dye-enhanced photothermal tumor therapy with a naphthalocyanine derivative.

Chromophore-enhanced photothermal therapy involves the application of an exogenous chromophore in combination with irradiation, using an appropriate wavelength, exposure duration and sufficient irradiances. 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. In an attempt to thermally damage tumor tissue with concurrent sparing of adjacent normal tissue, the potential of PdNc(OBu)8 for photothermal therapy was investigated. Using a Balb/c mouse model with subcutaneously implanted EMT6 adenocarcinoma, 90-100 hours after intraperitoneal application of PdNc(OBu)8, the tumor and surrounding tissue were irradiated with a 826nm continuous-wave diode laser. 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/cm-for 100 seconds, 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. 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 for chromophore-enhanced photothermal therapy.