Microdistributions of prospective BNCT-compound CuTCPH in tissue sections with heavy ion microbeam

P. STOLIAR; A. KREINER; M. DEBRAY; M. CARABALLO; A. VALDA; J. DAVIDSON; M. DAVIDSON; J. KESQUE; H. SOMACAL; H. DI PAOLO; A. BURLON; M. OZAFRÁN; M. VÁZQUEZ; D. MINSKY; E. HEBER; V. TRIVILLIN; A. SCHWINT

Boston, Massachusetts, Estados Unidos. Exposición oral (A.Kreiner)

Congreso; Eleventh World Congress on Neutron Capture Therapy; 2004

International Society for Neutron Capture Therapy

Introduction: The success of BNCT depends on our ability to deliver boron to tissuesusing one or more boron compounds to exert a therapeutic effect on tumor with scarcedamage to normal tissue. The efficacy of a boron compound will depend on its localization.Thus, the need for information on the microdistribution of the boron-carrier attissue and cellular level is critical in terms of testing new drugs, evaluating their therapeuticpotential and optimizing drug delivery strategies. The aim of the present studywas to evaluate the microdistribution of the carborane-containing tetraphenylporphyrinCuTCPH with one Cu atom in its molecular structure.Materials and Methods: The analytic technique employed in the present study is knownas micro-PIXE, namely Particle Induced X-ray Emission with beams of micrometer dimensions.It is based on the detection of characteristic X-rays of the elements in thesample, following the irradiation with a focused 16O ion beam. Focusing is performedwith a high-precision magnetic quadrupole triplet on freeze-dried cryosections of tumorand normal tissue from hamsters injected with the drug and of non-injected controls.Since B X-rays are extremely difficult to measure, advantage has been taken of thepresence of Cu in the porphyrin molecule. Exophytic tumors were induced on theright Cheek Pouch of Syrian Hamsters (HCP) in keeping with the HCP carcinogenesismodel of oral cancer previously validated for BCNT research. Samples from tumor,precancerous tissue surrounding tumor, normal contralateral pouch and liver (both forinjected and non-injected animals as controls) were taken.Results: Two-dimensional maps of elemental concentration were obtained by scanningthe beam over the sample. The results for Cu can be translated into B concentrations(the B/Cu mass ratio in CuTCPH is 6.805). The average B concentration in a tumorsample over a large 2 x 2 mm2 field was 116±46 ug/g with hot spots of up to 422ug/g. Maximum and minimum concentrations in a series of 1 x 1 mm2 tumor sectionswere 184 and 68 ug/g. Concentration in liver was high (694 ug/g). For precanceroustissue we obtained two widely different values for different regions (13 and 299 ug/g ata hot spot). A value for a section of normal contralateral HCP tissue was 35 ug/g.Discussion: Very inhomogeneous concentrations were found in all sections (exceptin liver tissue). The Cu (and hence the CuTCPH and the associated B to the extentthat the drug is stable) localizes preferentially in tumor as compared to normal tissue.Within tumor, it appears to localize selectively in tumor stroma (connective tissue)rather than in tumor parenchyma. In particular, it may be associated to blood vessels.Conclusions: The microPIXE technique, as implemented with an 16O microbeam, hasbeen shown to be a powerful analytical tool for the study of multielemental distributionsin histological sections at the few ug/g level. In particular its application for thedetermination of microdistributions of a drug of possible relevance for BNCT has beendemonstrated. CuTCPH appears to be localized preferentially in tumor stroma.