Evaluation of the New Photosensitizer Tookad (WST09) for Photodynamic Vessel Occlusion of the Choroidal Tissue in Rabbits

Framme, Carsten; Sachs, Helmut; Flucke, Barbara; Theisen-Kunde, Dirk; Birngruber, Reginald

doi:10.1167/iovs.06-0532

Cited by 8 publications

(12 citation statements)

References 28 publications

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“…[31][32][33] Benzoporphyrin derivative (BPD), also known as verteporfin, has an absorption maximum of 692 nm and is approved worldwide for the treatment of age-related macular degeneration. 12 The wavelength of 780 nm was chosen to correspond to the absorption of some emerging photosensitizers, such as TOOKAD 34 and others still in preclinical development, 35 which are designed to take advantage of increased penetration of light in this spectral range. Based on our findings, these next-generation sensitizers with high absorption at 780 nm and beyond would be favorable candidates for clinical trials of interstitial PDT of renal cancers.…”

Section: Discussionmentioning

confidence: 99%

Optical property measurements establish the feasibility of photodynamic therapy as a minimally invasive intervention for tumors of the kidney

et al. 2012

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Abstract. We measured the optical properties of freshly excised kidneys with renal parenchymal tumors to assess the feasibility of photodynamic therapy (PDT) in these patients. Kidneys were collected from 16 patients during surgical nephrectomies. Spatially resolved, white light, steady-state diffuse reflectance measurements were performed on normal and neoplastic tissue identified by a pathologist. Reflectance data were fit using a radiative transport model to obtain absorption (μ a ) and transport scattering coefficients (μ 0 s ), which define a characteristic light propagation distance, δ. Monte Carlo (MC) simulations of light propagation from cylindrical diffusing fibers were run using the optical properties extracted from each of the kidneys. Interpretable spectra were obtained from 14 kidneys. Optical properties of human renal cancers exhibit significant inter-lesion heterogeneity. For all diagnoses, however, there is a trend toward increased light penetration at longer wavelengths. For renal cell carcinomas (RCC), mean values of δ increase from 1.28 to 2.78 mm as the PDT treatment wavelength is increased from 630 to 780 nm. MC simulations of light propagation from interstitial optical fibers show that fluence distribution in tumors is significantly improved at 780 versus 630 nm. Our results support the feasibility of PDT in selected renal cancer patients, especially with photosensitizers activated at longer wavelengths.

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Section: Discussionmentioning

confidence: 99%

Optical property measurements establish the feasibility of photodynamic therapy as a minimally invasive intervention for tumors of the kidney

et al. 2012

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“…The absorption coefficient is 10 5 . Derived from previous investigations [17], the dye concentration injected through the ear vein was chosen to be 5 mg/kg of body weight. The PDT lesions were made within 5–15 min after dye injection using an argon laser pumped wavelength tunable titanium sapphire laser.…”

Section: Methodsmentioning

confidence: 99%

“…It was our primary purpose to develop a rabbit CNV model for investigating the potential of the new photosensitizer Tookad for PDT [17]. It is based on a bacteriochlorophyll, i.e.…”

Section: Introductionmentioning

confidence: 99%

“…After intravenous administration, Tookad becomes mainly bound to high-density and low-density lipoproteins. Further advantageous characteristics of this substance and its interaction with the rabbit’s choroid were extensively described before [17]. …”

Section: Introductionmentioning

confidence: 99%

“…Secondly, the amount of retinal tissue destruction should be critically reevaluated, and thirdly, in a preliminary approach, angiographically determined CNVs should be treated by experimental Tookad PDT [17]. …”

Section: Introductionmentioning

confidence: 99%

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Clinical Evaluation of Experimentally Induced Choroidal Neovascularizations in Pigmented Rabbits by Subretinal Injection of Lipid Hydroperoxide and Consecutive Preliminary Photodynamic Treatment with Tookad

Framme

Sachs²,

Kobuch³

et al. 2008

Ophthalmologica

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Purpose: Up to date several approaches have been undertaken to achieve an ‘easy-to-handle’ animal model of choroidal neovascularizations (CNVs) in rabbits; however, so far in none of the studies could healthy retinal tissue be maintained, which is mandatory to further investigate the effects of photodynamic therapy (PDT) or anti-vascular-endothelial-growth-factor treatments. It was our aim to reevaluate and verify the method of inducing experimental CNVs in rabbits using subretinally injected linoleic acid hydroperoxide (LHP) as proposed by Tamai et al. and to use it for experimental PDT. Material and Methods: In 33 eyes of Chinchilla breed rabbits LHP of two different concentrations (25 and 100 µg/50 µl) was injected into the subretinal space via a transvitreal approach under guidance of an operation microscope. Ophthalmoscopic and angiographic examinations were performed on days 3, 7, 14 and 28 after surgery. Preliminary PDT with different experimental parameter sets was performed in 3 eyes using the new photosensitizer Tookad. Results: Using LHP in the higher concentration, an angiographically determined CNV induction was observed in 27% of all injection sites (n = 34) on days 14 and 28 revealing early well-demarcated and progressive leakage. No CNV was detected at the lower LHP concentration (60 injection sites). Subretinal CNV was verified histologically revealing vessel formation above the retinal pigment epithelium level. Herein, a significant damage to the outer retinal layers was always observed; however, the general structure of the choriocapillary layer was maintained. Tookad PDT was clinically able to completely stop leakage in 1 case and reduce leakage in 2 cases. Histologically the choriocapillary layer was occluded. Conclusion: Subretinal injection of LHP induces angiographically well-demarcated classic CNVs in rabbits; however, the CNV rate was low, and histology revealed severe damage of the outer retinal layers but not of the choriocapillary layer, which is important for studying PDT interactions. Preliminary experimental PDT could clinically stop or reduce leakage from angiographic CNV. Due to the small CNV rate and the significant collateral retinal tissue damage, this model seems to be only of partial suitability for investigating new treatment modalities in CNV.

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A novel recombinant chlorophyllase from cyanobacterium Cyanothece sp. ATCC 51142 for the production of bacteriochlorophyllide a

Chou

Lee

Yen

et al. 2015

Biotech and App Biochem

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Bacteriopheophorbide a (BPheid a) is used as a precursor for bacteriochlorin a (BCA), which can be used for photodynamic therapy in both in vitro and in vivo biochemical applications. This study successfully isolated and expressed a photosynthetic bacterium (Cyanothece sp. ATCC 51142) chlorophyllase called CyanoCLH, which can be used as a biocatalyst for the production of a BCA precursor by degrading bacteriochlorophyll a (BChl a). Substrate specificity and enzyme kinetic analyses were performed and the results verified that the recombinant CyanoCLH preferred hydrolyzing BChl a to produce bacteriochlorophyllide a (BChlide a), which can be converted to BPheid a by removing magnesium ion. The recombinant CyanoCLH was cloned and expressed in Escherichia coli BL-21 (DE3), and its molecular weight was 54.7 kDa. The deduced amino acid sequence of the recombinant CyanoCLH comprised a unique lipase-motif GHSLG, which differs from the GHSRG sequence of other plants and lacks a histidine of the typical and conserved catalytic triad Ser-Asp-His. The recombinant CyanoCLH was subjected to biochemical analyses, and the results indicated that its optimal pH and temperature were 7.0 and 60 °C, respectively.

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Evaluation of the New Photosensitizer Tookad (WST09) for Photodynamic Vessel Occlusion of the Choroidal Tissue in Rabbits

Cited by 8 publications

References 28 publications

Optical property measurements establish the feasibility of photodynamic therapy as a minimally invasive intervention for tumors of the kidney

Optical property measurements establish the feasibility of photodynamic therapy as a minimally invasive intervention for tumors of the kidney

Clinical Evaluation of Experimentally Induced Choroidal Neovascularizations in Pigmented Rabbits by Subretinal Injection of Lipid Hydroperoxide and Consecutive Preliminary Photodynamic Treatment with Tookad

A novel recombinant chlorophyllase from cyanobacterium Cyanothece sp. ATCC 51142 for the production of bacteriochlorophyllide a

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