Photochemical internalization of bleomycin before external-beam radiotherapy improves locoregional control in a human sarcoma model.
OBJECTIVE
The aim of this study was to explore the tumor growth response of the combination photochemical internalization and external-beam radiotherapy. Photochemical internalization is a technology to improve the utilization of therapeutic macromolecules in cancer therapy by photochemical release of endocytosed macromolecules into the cytosol.


METHODS
A human sarcoma xenograft TAX-1 was inoculated subcutaneously into nude mice. The photosensitizer AlPcS(2a) and bleomycin were intraperitoneally administrated 48 h and 30 min, respectively, before diode laser light exposure at 670 nm (20 J/cm(2)). Thirty minutes or 7 days after photochemical treatment, the animals were subjected to 4 Gy of ionizing radiation.


RESULTS
Using photochemical internalization of bleomycin as an adjunct to ionizing radiation increased the time to progression for the tumors from 17 to 33 days as compared with that observed with photodynamic therapy combined with ionizing radiation as well as for radiochemotherapy with bleomycin. The side effects observed when photochemical internalization of bleomycin was given shortly before ionizing radiation were eliminated by separating the treatment modalities in time.


CONCLUSIONS
Photochemical internalization of bleomycin combined with ionizing radiation increased the time to progression and showed minimal toxicity and may therefore reduce the total radiation dose necessary to obtain local tumor control while avoiding long-term sequelae from radiotherapy.
Norum
Ole-Jacob
OJ
Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, Oslo, Norway. oleno@radiumhospitalet.no
Bruland
Øyvind Sverre
ØS
Gorunova
Ludmila
L
Berg
Kristian
K
D000818:Animals; D001761:Bleomycin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy / Q000379:methods; D018450:Disease Progression; D004705:Endocytosis; D005260:Female; D006801:Humans; D007211:Indoles / Q000493:pharmacokinetics / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use; D055668:Photochemical Processes; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011833:Radiation Injuries, Experimental / Q000503:physiopathology; D011836:Radiation Tolerance / Q000187:drug effects; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011897:Random Allocation; D012509:Sarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects / Q000528:radiation effects; D023041:Xenograft Model Antitumor Assays
D007211:Indoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D011838:Radiation-Sensitizing Agents; D001761:Bleomycin; C064331:aluminum phthalocyanine disulfonate