Boron neutron capture therapy for undifferentiated thyroid carcinoma: preliminary results with the combined use of BPA and BOPP.

Department of Radiobiology, Constituyentes Atomic Center, Av del Libertador 8250, 1429 Buenos Aires, Argentina.
Applied Radiation and Isotopes (Impact Factor: 1.06). 12/2004; 61(5):905-9. DOI: 10.1016/j.apradiso.2004.05.005
Source: PubMed

ABSTRACT We have shown the selective uptake of borophenylalanine (BPA) by undifferentiated human thyroid cancer (UTC) ARO cells both in vitro and in vivo. Moreover, a 50% histologic cure of mice bearing the tumor was observed when the complete boron neutron capture therapy was applied. More recently we have analyzed the biodistribution of BOPP (tetrakis-carborane carboxylate ester of 2,4-bis-(alpha,beta-dihydroxyethyl)-deutero-porphyrin IX) and showed that when BOPP was injected 5 days before BPA, and the animals were sacrificed 60 min after the i.p. injection of BPA, a significant increase in boron uptake by the tumor was found (38-45 ppm with both compounds vs. 20 ppm with BPA alone). Five days post the i.p BOPP injection and 1h after BPA the ratios were: tumor/blood 3.75; tumor/distal skin 2. Other important ratios were tumor/thyroid 6.65 and tumor/lung 3.8. The present studies were performed in mice transplanted with ARO cells and injected with BOPP and BPA. Only in mice treated with the neutron beam and injected with the boronated compounds we observed a 100% control of tumor growth. Two groups of mice received different total absorbed doses: 3.00 and 6.01 Gy, but no further improvement in the outcome was found compared to the previous results using BPA alone (4.3 Gy).

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    ABSTRACT: Purpose of review: Undifferentiated thyroid carcinoma (anaplastic thyroid carcinoma) is an aggressive tumor with a poor prognosis. Experimental data are collected to support the expansion to undifferentiated thyroid carcinoma of boron neutron capture therapy. Recent findings: Boron neutron capture therapy has been applied to glioblastoma and melanoma. Studies of boron neutron capture therapy in a human anaplastic thyroid carcinoma cell line in vitro and in tumor-bearing nude mice have shown that uptake of 10B compounds can be fostered that is sufficient to cause tumor growth arrest, cell death, or both. There is preferential uptake of boron compounds by tumor cells compared with noncancerous cells. Additional preclinical information is required about the biodistribution of candidate boron compounds in humans and about possible adverse effects of boron neutron capture therapy on critical nonthyroidal structures of the neck. Summary: Boron neutron capture therapy has promise as a management tool for aggressive cancers, including undifferentiated thyroid carcinoma, that are not responsive to conventional radiotherapy or chemotherapy.
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    ABSTRACT: Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Nuclear Science and Engineering, 2008. "June 2008." Includes bibliographical references. Boron neutron capture therapy (BNCT) is a biochemically targeted form of radiotherapy for cancer. In BNCT, a compound labeled with the stable isotope boron-10 is systemically administered, and tumor cells selectively uptake the boron-10 containing compound at higher concentrations than normal cells. A general problem with the tumor seeking compounds is that drug delivery is dependent upon sufficient vascularization within the tumor. To investigate the possibility of delivering boron to hypoxic regions of tumor, a new boronated nitroimidazole delivery agent has been synthesized as a carrier of boron-10 for BNCT. It is expected that this will be used in combination with the existing boron carrier boronophenylalanine-fructose to treat solid tumors. An immunohistochemical protocol to visualize hypoxia was tested and refined to confirm the suitability of two tumor models established in the lab for hypoxia related uptake studies. The immunohistochemical protocol is used to detect pimonidazole, which localizes at hypoxic regions in tissue and is the parent compound for the new hypoxia-selective boron carrier. The protocol was used to test and confirm the suitability of a hypoxic in vivo tumor model. Two tumor lines were tested: SCCVII squamous cell carcinoma and EMT-6 murine mammary carcinoma. Both exhibited hypoxia. Finally, quantitative studies using Inductive Coupled Plasma Atomic Emission Spectrum demonstrated that the synthesized boronated nitroimidazole reaches suitable concentrations in SCCVII and F98 tumor. Future therapeutic studies are required to empirically confirm the effectiveness of this compound. by Jugal Shah. S.B.

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