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Photodynamic therapy as novel nephron sparing treatment option for small renal masses
Stephanie G C Kroeze1, Mathijs C M Grimbergen, Holger Rehmann
1Department of Urology, University Medical Center Utrecht, Utrecht, The Netherlands.
Purpose:
Photodynamic therapy has great potential as nephron sparing therapy for small renal masses. Using mTHPC [meso-tetra(hydroxyphenyl)chlorin] (BioLitec Pharma, Dublin, Ireland), a photosensitizer that targets vasculature and tissue, we determined whether renal tumors could be ablated using mTHPC mediated photodynamic therapy in a translational renal carcinoma mouse model.
Materials And Methods:
We administered mTHPC intravenously in kidney tumor bearing mice. Tumor diameter was about 7 mm. At several drug-light intervals a cylindrical laser fiber was placed intratumorally for interstitial illumination using a wavelength of 652 nm. We determined mTHPC biodistribution up to 48 hours after administration and tumor destruction after mTHPC mediated photodynamic therapy. In vitro mTHPC uptake and photodynamic therapy induced cytotoxicity were studied in human endothelial, renal and renal cell carcinoma cell lines.
Results:
Ablated regions with a maximum diameter of 9.3 mm and complete loss of cell viability were observed at a drug-light interval of 4 hours, when mTHPC was increased in blood and tissue. Viable renal tissue remained detectable outside the illuminated area. In endothelial cells mTHPC uptake and sensitivity to photodynamic therapy were increased compared to those in renal cell carcinoma and renal cells.
Conclusions:
mTHPC mediated photodynamic therapy is a nephron sparing therapy. The extent of renal tumor destruction is adequate for clinical translation. Localization of mTHPC in tumor vasculature and tissue produces a strong combined effect. Our findings justify further preclinical studies of the applicability of photodynamic therapy for renal cell carcinoma before photodynamic therapy can become a valuable addition to current minimally invasive treatments of small renal masses.
Insights
Photodynamic therapy using meso-tetra(hydroxyphenyl)chlorin (mTHPC) effectively ablated renal tumors in mice. This nephron-sparing approach shows promise for treating small renal masses, warranting further clinical studies.
Area of Science:
- Oncology
- Medical Physics
- Pharmacology
Background:
- Photodynamic therapy (PDT) offers potential for nephron-sparing treatment of small renal masses.
- Meso-tetra(hydroxyphenyl)chlorin (mTHPC) is a photosensitizer targeting tumor vasculature and tissue.
Purpose of the Study:
- To evaluate the efficacy of mTHPC-mediated PDT for ablating renal tumors in a preclinical mouse model.
- To assess mTHPC biodistribution and tumor destruction following PDT.
Main Methods:
- Mice with renal tumors received intravenous mTHPC. Intratumoral laser illumination (652 nm) was applied at various drug-light intervals.
- mTHPC biodistribution, tumor destruction, and in vitro cellular responses were analyzed.
Main Results:
- Complete tumor cell ablation (up to 9.3 mm diameter) was achieved at a 4-hour drug-light interval, correlating with increased mTHPC in blood and tissue.
- Viable renal tissue was preserved outside the illuminated zone.
- Endothelial cells exhibited higher mTHPC uptake and PDT sensitivity than renal cell carcinoma and renal cells.
Conclusions:
- mTHPC-mediated PDT is a viable nephron-sparing therapy for renal tumors.
- The observed tumor destruction is adequate for clinical translation.
- mTHPC's localization in tumor vasculature and tissue enhances its therapeutic effect, supporting further preclinical investigation for renal cell carcinoma treatment.
