碳-11標誌1-Aminocyclobutane carboxylic acid (ACBC)已由文獻報導對再復發性腦腫瘤診斷造影具有高精確度，此胺基酸在腦腫瘤正常組織的吸收比值可達10：1。本研究欲探討含硼的ACBC胺基酸衍生物1-Amino-3-(4-boronophenyl)cyclobutane carboxylic acid以做為治療腦癌或肝癌之BNCT化合物。論文主題在於此含硼胺基酸化合物之合成，並針對肝癌細胞與腦癌細胞，進行化學毒性及細胞吸收的測試。
1-Amino-3-(4-boronophenyl)cyclobutane carboxylic acid經由七個步驟之合成，起始物4-Bromostyrene可由市面商品購得，關鍵性的步驟為第一步及第二步的合成，此兩步之反應試劑在反應過程對水份子相當敏感，易造成反應不完全而導致產率過低；第六步及第七步經由Bucherer-Strecher反應後可得最終產物，惟最終產物尚含NaCl待進一步純化。以上各合成之化合物及最終產物皆經由1H-NMR及13C-NMR鑑定確認。

本實驗研究目的即利用所合成之3-(4-Boronophenyl)cyclo

butanone（compound Ⅵ）及1-Amino-3-(4-boronophenyl)cyclobutane carboxylic acid（compound Ⅷ）化合物進行腦癌細胞（G5T/VGH及GBM8901）與肝癌細胞（HepG2）吸收試驗，分別探討最大致死劑量（LD50）、毒性測試及吸收度測試，以期未來此藥物應用於動物實驗乃至臨床試驗之基礎參考依據。

由結果顯示，比較此兩種含硼化合物對癌細胞的毒性，硼化合物Ⅵ要比硼胺基酸化合物Ⅷ對癌細胞較具毒性，要達50%的致死劑量，以HepG2細胞而言，前者使用最大劑量為150 ppm，而後者的使用最大劑量可達約1000 ppm。以GBM8901細胞而言，前者藥物最大劑量為400 ppm，而後者則可達3000 ppm。以G5T/VGH細胞而言，前者最大劑量為200 ppm，而後者則最大劑量可達700 ppm。

對於細胞吸收實驗，由數據看出，肝癌細胞HepG2對硼化合物Ⅵ的吸收隨時間逐漸升高，對硼胺基酸化合物Ⅷ卻不吸收。腦癌細胞GBM8901、G5TVGH則呈現相反趨勢，對硼化合物Ⅵ不見有吸收，對硼胺基酸化合物Ⅷ則有顯著的吸收，由以上結果顯現硼化合物Ⅵ於肝癌BNCT治療的應用有極高的潛力 ; 而硼胺基酸化合物Ⅷ則對腦癌細胞BNCT治療有極高的潛力。硼化合物Ⅵ及硼胺基酸化合物Ⅷ分別對肝癌細胞及腦癌細胞之吸收量達到1013 10B /cell以上，顯現出未來應用於肝癌與腦癌BNCT治療之潛力。

11C-1-aminocyclobutane carboxylic acid (ACBC) an unnatural cyclic amino carboxylic acid, has been reported previously to be high accurate in determining recurrent brain tumors. This work has synthesized a lipophilic boron-containing cyclic amino carboxylic acid, 1-amino-3-[7-(4-borophenyl)heptyl]cyclobutane carboxylic acid, analogous to ACBC, as a BNCT drug for treatment to brain tumors and hepatoma. In the present study, cell uptake of the boron-containing amino acid in hepatoma and glioblastoma has been investigated.
1-Amino-3-(4-boronophenyl)cyclobutane carboxylic acid has been successfully synthesized via 7 steps. The key synthetic process is pertinent to the initial two steps; the reaction will become incomplete and lead to very low product-yield if the moisture exists. The last two steps involve the preparation of properly substituted cyclobutanone followed by a Bucherer-Strecker amino acid synthesis. The final product in a mixture with NaCl is tried to purify by a silica gel column chromatography. All products were identified by 1H-NMRand13C-NMR.

The products obtained from the synthesis 3-(4-boronophenyl)

cyclobutanone(compound Ⅵ) and 1-amino-3-(4-boronophenyl)cyclo

-butanecarboxylic acid(compound Ⅷ) were taken for the cell uptake test by glioblastoma （G5T/VGH and GBM8901 tumor cell）and hepatoma（HepG2 tumor cell）. Experiments with respect to maximal lethal dose (LD50), chemical toxicity, radiation damage, and cell uptake extent are conducted.

Comparing the toxicity of both boron containing compounds, the 50% lethal dose of 3-(4-boronophenyl)cyclobutanone (Ⅵ) for the tumor cells of either hepatoma or glioblastoma is generaly lower than 1-amino-3-(4-boronophenyl)cyclobutane carboxylic acid(Ⅷ). For HepG2 cells, 50% lethal dose for compound Ⅵ is 150 ppm, while for compound Ⅷ is 1000 ppm. For GBM8901 cells, 50% lethal dose for compound Ⅵ is 400 ppm, while for compound Ⅷ is 4000 ppm. For G5TVGH cells, 50% lethal dose for compound Ⅵ is 200 ppm, while for compound Ⅷ is 700 ppm.

The uptake of compound Ⅵ by HepG2 cells was observed to increase with increasing the elapsed time, reaching 2.7×1014 B/cell at 48 h, while the uptake of compound Ⅷ by HepG2 cells was negligible. By contrast, the uptake of compound Ⅷ by GBM8901 cells was observed to increase initially to 4×1013 B/cell at 3 h and then decrease with increasing the elapsed time to 6.5×1011 B/cell at 48h. While the uptake of compound Ⅷ by G5T/VGH cells was observed to increase initially to 7.47×1012 B/cell at 6 h and then decrease with increasing the elapsed time to 3.59×1012 B/cell at 24h. From the results, it is revealed that compound Ⅵ may possess the potential as hepatoma BNCT drug, while compound Ⅷ may have the potential as glioblastoma BNCT drug.

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