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Jeffrey A. Coderre and Otto K. Harling. Chung, Yoonsun Massachusetts Institute of Technology. Dept. of Nuclear Science and Engineering. Massachusetts Institute of Technology. Department of Nuclear Science and Engineering 2009-03-16T19:42:37Z 2009-03-16T19:42:37Z 2008 2008 http://hdl.handle.net/1721.1/44784 300300740 Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Nuclear Science and Engineering, 2008. Includes bibliographical references (p. 123-132). This thesis evaluates the radiobiological effectiveness of three new boron compounds namely a boronated porphyrin (BOPP) and two liposome formulations for neutron capture therapy (BNCT). The methodology utilizes in vitro and in vivo comparisons that characterize compounds relative to boric acid and boronophenylalanine (BPA). In vitro evaluations utilized a colorimetric assay and 96-well plates to minimize the quantities of compound required for testing. The assay was optimized for the murine SCCVII, squamous cell carcinoma to determine the chemical toxicity and relative cellular uptake of a compound. BOPP was toxic at low concentrations and comparisons between the different compounds for thermal neutron irradiations were performed with approximately 5 [mu]g 10B/ml in the culture medium to allow radiation induced effects to govern the observed response. Using less than 300 [mu]g of compound and 250 kVp X-rays as control irradiations, a compound biological effectiveness (CBE) of 3.3 ± 0.7 was determined for BOPP that is comparable to the result for boric acid (3.5 ± 0.5) indicating a non-selective intracellular accumulation of 10B. BPA has a significantly higher CBE of 6.1 + 0.7. Boronated liposomes (MAC-16 and MAC+TAC) were evaluated with the EMT-6 murine mammary carcinoma. Biodistribution studies showed high 10B uptake in tumor (20-40 [mu]g 10B/g) 30 hours after a single i.v. injection (dose 6-20 [mu]g 10B per gram of body weight). Tumor control experiments were performed using thermal neutrons to study the efficacy of the boron delivered by liposomes and BPA. The MAC-16 produced a 16 % tumor control and BPA (dose 43 [mu]g 10B/gbw) 63 % for tumor boron concentrations of approximately 20 [mu]g 10B/g and the same neutron fluence. (cont.) Liposome doses were limited by injection volume and so two injections were tried 2-hours apart that doubled the boron concentration in tumor compared to a single administration. This improved the therapeutic response to 67 % with less apparent skin damage than with BPA. Microscopic studies using fluorescent labeled liposomes revealed 10B was nonuniformly distributed and concentrated at the edge of the tumor. Based on these studies in the tumor cell lines chosen neither of the compounds appear superior to BPA. by Yoonsun Chung. Ph.D. 132 p. eng Massachusetts Institute of Technology M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 Nuclear Science and Engineering. Radiobiological evaluation of new boron delivery agents for boron neutron capture therapy Thesis application/pdf false Publication unknown unknown <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="8c94de2a-0499-45fb-91ed-4c66635acf17"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Language>eng</Language> <Title>Radiobiological evaluation of new boron delivery agents for boron neutron capture therapy</Title> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2008</PublicationDate> <Authors> <Author> <DisplayName>Chung, Yoonsun</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Massachusetts Institute of Technology</DisplayName> <OrgUnit /> </Publisher> </Publishers> <License>http://dspace.mit.edu/handle/1721.1/7582</License> <Keyword>Nuclear Science and Engineering.</Keyword> <Abstract>This thesis evaluates the radiobiological effectiveness of three new boron compounds namely a boronated porphyrin (BOPP) and two liposome formulations for neutron capture therapy (BNCT). The methodology utilizes in vitro and in vivo comparisons that characterize compounds relative to boric acid and boronophenylalanine (BPA). In vitro evaluations utilized a colorimetric assay and 96-well plates to minimize the quantities of compound required for testing. The assay was optimized for the murine SCCVII, squamous cell carcinoma to determine the chemical toxicity and relative cellular uptake of a compound. BOPP was toxic at low concentrations and comparisons between the different compounds for thermal neutron irradiations were performed with approximately 5 [mu]g 10B/ml in the culture medium to allow radiation induced effects to govern the observed response. Using less than 300 [mu]g of compound and 250 kVp X-rays as control irradiations, a compound biological effectiveness (CBE) of 3.3 ± 0.7 was determined for BOPP that is comparable to the result for boric acid (3.5 ± 0.5) indicating a non-selective intracellular accumulation of 10B. BPA has a significantly higher CBE of 6.1 + 0.7. Boronated liposomes (MAC-16 and MAC+TAC) were evaluated with the EMT-6 murine mammary carcinoma. Biodistribution studies showed high 10B uptake in tumor (20-40 [mu]g 10B/g) 30 hours after a single i.v. injection (dose 6-20 [mu]g 10B per gram of body weight). Tumor control experiments were performed using thermal neutrons to study the efficacy of the boron delivered by liposomes and BPA. The MAC-16 produced a 16 % tumor control and BPA (dose 43 [mu]g 10B/gbw) 63 % for tumor boron concentrations of approximately 20 [mu]g 10B/g and the same neutron fluence.</Abstract> <Abstract>(cont.) Liposome doses were limited by injection volume and so two injections were tried 2-hours apart that doubled the boron concentration in tumor compared to a single administration. This improved the therapeutic response to 67 % with less apparent skin damage than with BPA. Microscopic studies using fluorescent labeled liposomes revealed 10B was nonuniformly distributed and concentrated at the edge of the tumor. Based on these studies in the tumor cell lines chosen neither of the compounds appear superior to BPA.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>