Tissue-localizing properties of some photosensitizers studied by in vivo fluorescence imaging

Leengoed, Eric van; Versteeg, Jeanne A.C.; Veen, Nynke van der; Berg-Blok, A. Van Den; Marijnissen, H.; Star, Willem M.

doi:10.1016/1011-1344(90)85080-g

Cited by 22 publications

(9 citation statements)

References 12 publications

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“…These data are in good agreement with our previous findings in human LOX tumour tissue transplanted in nude mice (Peng et al, 1991a(Peng et al, , 1993. Similar results were also found by others in mammary carcinoma of WAG/RIJ rats by the use of a transparent observation chamber system (van Leengoed et al, 1990(van Leengoed et al, , 1993b.…”

Section: Animals and Twnour Linesupporting

confidence: 77%

Correlation of distribution of sulphonated aluminium phthalocyanines with their photodynamic effect in tumour and skin of mice bearing CaD2 mammary carcinoma

Peng

Moan²

1995

Br J Cancer

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Summan-A chemical extraction assax-and fluorescence microscopi incorporating a light-sensitive thermoelectnically cooled charge-coupled device (CCD) camera was used to study the kinetics of uptake. retention and localisation of disulphonated aluminium phthalocyanine (AIPcS-) and tetrasulphonated aluminium phthalocvanine (AlPcS4) at different time inten-als after an i.p. injection at a dose of 10 mg kg`body w-eight (b.Ax in tumour and surrounding normal skin and muscle of female C-D F, mice bearing CaD2 mammary carcinoma. Moreover. the photodymamic effect on the tumour and normal skin using sulphonated aluminium phthalocvanines (AIPcS,. AIPcS:. AlPcS4) and Photofrin was compared w-ith respect to dye, dve dose and time interval betu-een dve administration and light exposure. The maximal concentrations of AlPcS in the tumour tissue w-ere reached 2-24 h after injection of the dve. while the amounts of AIPcS4 peaked 1-2 h after the dve administration. AlPcS, was simultaneouslv localised in the interstitium and in the neoplastic cells of the tumour. uhereas AlPcS4 appeared to localise only in the stroma of the tumour. The photodynamic efficiency (light A-as applied 24 h after dye injection at a dose of 10 mg kg-' b.wu. of the tumours u-as found to decrease in the folloWing order: AlPcS > AIPcS4> Photofrin > AlPcSl. Furthermore. photodynamic efficacyv was strongly dependent upon dye doses and time intervals betw-een dye administration and light exposure: the higher the dose. the higher the photodynamic efficiency. The most efficient photodynamic therapy (PDT) of the tumour u-as reached (day 20 tumour-free) when light exposure took place 2 h after injection of AlPcS, (10 mg k-.) A dual intratumoral localisation pattern of the dye. as found for AlPcS:. seems desirable to obtain a high photodynamic efficiency. The kinetic patterns of uptake. retention and localisation of AlPcS, and AIPcS4 are roughly correlated w-ith their photodynamic effect on the tumour and normal skin.

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Section: Animals and Twnour Linesupporting

confidence: 77%

Correlation of distribution of sulphonated aluminium phthalocyanines with their photodynamic effect in tumour and skin of mice bearing CaD2 mammary carcinoma

Peng

Moan²

1995

Br J Cancer

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“…Recently, there has been an increased interest in the use of photosensitizers with in vivo imaging modalities to provide a common system for simultaneous imaging and therapy (11)(12)(13). MRI is a non-invasive imaging modality and has several advantages over other imaging modalities since it provides three-dimensional anatomic images with high spatial resolution.…”

Section: Introductionmentioning

confidence: 99%

Contrast-Enhanced MRI-Guided Photodynamic Cancer Therapy with a Pegylated Bifunctional Polymer Conjugate

et al. 2008

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Purpose-To study contrast-enhanced MRI guided photodynamic therapy with a pegylated bifunctional polymer conjugate containing an MRI contrast agent and a photosensitizer for minimally invasive image-guided cancer treatment.Methods-Pegylated and non-pegylated poly-(L-glutamic acid) conjugates containing mesochlorin e 6 , a photosensitizer, and Gd(III)-DO3A, an MRI contrast agent, were synthesized. The effect of pegylation on the biodistribution and tumor targeting was non-invasively visualized in mice bearing MDA-MB-231 tumor xenografts with MRI. MRI-guided photodynamic therapy was carried out in the tumor bearing mice. Tumor response to photodynamic therapy was evaluated by dynamic contrast enhanced MRI and histological analysis.Results-The pegylated conjugate had longer blood circulation, lower liver uptake and higher tumor accumulation than the non-pegylated conjugate as shown by MRI. Site-directed laser irradiation of tumors resulted in higher therapeutic efficacy for the pegylated conjugate than the nonpegylated conjugate. Moreover, animals treated with photodynamic therapy showed reduced vascular permeability on DCE-MRI and decreased microvessel density in histological analysis.Conclusions-Pegylation of the polymer bifunctional conjugates reduced non-specific liver uptake and increased tumor uptake, resulting in significant tumor contrast enhancement and high therapeutic efficacy. The pegylated poly(L-glutamic acid) bifunctional conjugate is promising for contrast enhanced MRI guided photodynamic therapy in cancer treatment.

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“…At 24 h p.i. tumour and blood vessel ratios become indistinguishable from the normal tissue, similar to what is observed with HpD in the same model (van Leengoed et al, 1990). A six fold reduction of the light dose to 100 J cm-2 (100 mW cm-2) was chosen as a higher overall concentration of the photosensitiser was expected.…”

Section: Methodsmentioning

confidence: 70%

“…a suitable time interval between dye administration and PDT. This is different from HpD-PDT, where in this observation chamber model, 2 h p.i., tumour fluorescence could be discriminated from normal tissue in only 40-50% of the cases (van Leengoed et al, 1990). In this model complete necrosis required a light dose of 160 J cm-2 at 630 nm applied 24 h p.i.…”

Section: Methodsmentioning

confidence: 97%

Fluorescence and photodynamic effects of bacteriochlorin a observed in vivo in 'sandwich' observation chambers

Leengoed

Schuitmaker²,

Veen³

et al. 1993

Br J Cancer

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Bacteriochlorin a (BCA), a derivative of bacteriochlorphyll a, is an effective photosensitiser in vitro and in vivo. BCA has a major absorption peak at 760 nm where tissue penetration is optimal. This property, together with rapid tissue clearance promises minor skin photosensitivity. The tissue localising and photodynamic properties of BCA were studied using isogeneic RMA mammary tumours, transplanted into subcutaneous tissue in transparent 'sandwich' observation chambers on the back of WAG/Rij rats. The fluorescence kinetics following an i.v. administration of 20 mg kg-1 BCA was assessed in blood vessels, tumour and normal tissue. Subsequently, the development of vascular- and tissue damage after a therapeutic light dose (760 nm, 600 J cm-2) was observed. Fifteen minutes post injection (p.i.), the fluorescence of BCA in the tumour reached a plateau value of 2.5 times the fluorescence in the normal tissue. From 1 h post injection the tumour fluorescence diminished gradually; after 24 h, the tumour fluorescence signal did not exceed that of the normal tissue. Following photodynamic therapy (PDT), 24 h p.i., complete vascular stasis was observed 2 h post treatment in the tumour only, with subsequent recovery. The presence of viable tumour cells following PDT was assessed by histology and re-transplantation of treated tumour tissue from the chamber into the flank immediately or 7 days after treatment. In both cases tumour regrowth was observed. BCA-PDT (20 mg kg-1, 760 nm, 100 J cm-2) 1 h after BCA administration, an interval which gives the optimal differential between tumour and normal tissue, was sufficient to prevent tumour regrowth. However, this only occurred when re-transplantation was performed 7 days after PDT. During PDT, 1 h p.i., vascular damage in tumour and normal tissue was considerable. Complete vascular shut-down was observed in the tumour 2 h after therapy and in the surrounding tissues at 24 h. Circulation damage was associated with vascular spasm and occlusion probably due to thrombi formation. Oedema was notable, especially following PDT with 600 J cm-2 at 24 h p.i. Images Figure 1

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Tissue-localizing properties of some photosensitizers studied by in vivo fluorescence imaging

Cited by 22 publications

References 12 publications

Correlation of distribution of sulphonated aluminium phthalocyanines with their photodynamic effect in tumour and skin of mice bearing CaD2 mammary carcinoma

Correlation of distribution of sulphonated aluminium phthalocyanines with their photodynamic effect in tumour and skin of mice bearing CaD2 mammary carcinoma

Contrast-Enhanced MRI-Guided Photodynamic Cancer Therapy with a Pegylated Bifunctional Polymer Conjugate

Fluorescence and photodynamic effects of bacteriochlorin a observed in vivo in 'sandwich' observation chambers

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