3-7-dihydro-6-(4-(2-(n--(5-fluoresceinyl)thioureido)ethoxy)phenyl)-2-methylimidazo-(1-2-a)pyrazin-3-one and Neoplasms

During photodynamic therapy (PDT) it is important to monitor the treatment progress to achieve the intended therapeutic outcome. Chemiluminescence (CL) provides a sensitive and selective means for (1)O(2) detection. In our study, by comparing CL with the corresponding in situ PDT treatment protocols and the treatment effect, the results indicate that the treatment outcome for tumors was governed by a set of dosimetry factors with a rather complicated relationship, but there was a remarkable connection between tumor treatment effect and CL. In conclusion, CL can be used in in vivo PDT to determine the dose of tumor treatment and monitor the treatment threshold. By monitoring CL it is feasible to determine PDT dose to predict tumor treatment effect.

Topics: Animals; Cell Line, Tumor; Dihematoporphyrin Ether; Female; Fluoresceins; Imidazoles; Light; Luminescent Measurements; Mice; Mice, Inbred BALB C; Neoplasms; Photochemotherapy; Photosensitizing Agents; Singlet Oxygen

A novel method of photodynamic diagnosis of cancer mediated by chemiluminescence probe is presented. The mechanism for photodynamic therapy involves singlet oxygen ((1)O(2)) generated by energy transfer from photosensitizers. (1)O(2) can react with 3,7-dihydro-6-[4-[2-(N'-(5-fluoresceinyl)thioureido)ethoxy]phenyl]-2-methylimidazo[1,2-a]pyrazin-3-one sodium salt (FCLA), which is a Cypridina luciferin analog and a specific chemiluminescence probe for detecting (1)O(2) and superoxide (O(2)(-)). The reaction of FCLA and (1)O(2) can give emission with peak wavelength at about 532 nm. In the present study, FCLA was chosen as an optical reporter of (1)O(2) produced from the photosensitization reaction of hematoporphyrin derivative in model solution and in nude mice with transplanted mammary cancer. Photosensitized chemiluminescence from the reaction of FCLA with (1)O(2) was detected by a highly sensitive Intensified Charge-Coupled Device detector. The chemiluminescence was markedly inhibited by the addition of 10 mmol/l sodium azide (NaN(3)) to the model solution and minor effects were observed at the addition of 10 micromol/l superoxide dismutase, 20 mmol/l mannitol and 100 microg/ml catalase, respectively, thus indicating that (1)O(2) generation from photosensitization reaction mainly results in light emission. Experiments in vivo with tumor-bearing mice showed a clear chemiluminescence image of tumor. The study suggests that this novel method may be applicable to the diagnosis of superficial tumors.

Topics: Animals; Diagnostic Techniques and Procedures; Disease Models, Animal; Female; Fluoresceins; Hematoporphyrins; Imidazoles; Luminescent Measurements; Mice; Models, Chemical; Molecular Probes; Neoplasms; Photosensitizing Agents; Singlet Oxygen; Sodium Azide

In this work, the chemiluminescence method was engaged for the first time to detect the active oxygen species during sonodynamic action in vitro and in vivo. We used FCLA (3,7-dihydro-6-[4-[2-[N'-(5-fluoresceinyl)thioureido]-ethoxy]phenyl]-2-methylimidazo[1,2-a]pyrazin-3-one sodium salt), which can selectively react with singlet oxygen ((1)O(2)) or superoxide anion (O(2)(-)) to emit photons, to detect in real time oxygen free radical formation in the sonosensitization of hematoporphyrin derivative. The results show that (1)O(2) is involved in the sonosensitization. In in vivo experiments, a tumor-imaging method by sonodynamic chemiluminescence detection was established. This method could have potential applications in clinics for tumor diagnosis.

Topics: Fluoresceins; Free Radical Scavengers; Humans; Imidazoles; Luminescent Measurements; Neoplasms; Photons; Reactive Oxygen Species; Sensitivity and Specificity; Singlet Oxygen; Superoxides