近年來由於核醫標靶治療(targeted therapy)的快速發展，其中以可加強毒殺癌細胞效果的(Radioimmunotherapy, RIT)更令人感興趣，但由於其是利用單株抗體(monoclonal antibody, MoAb)將放射性核種帶至腫瘤細胞所在處，使得傳統核醫劑量評估使用之器官劑量學(organ dosimetry)已不敷用，而必須改為細胞及分子劑量評估所用之微劑量學(microdosimetry)及奈米劑量學(nanodosimetry)，針對生物敏感(biological sensi- tive)之微奈米靶區(target region)，進行有關輻射劑量及輻射品質的評估。放射免疫治療多使用分布於細胞表面或細胞內之短射程輻射粒子的放射性核種，譬如釋出低能量貝他粒子或鄂惹電子等核種，使之與腫瘤細胞相結合，然後利用這些輻射粒子射程短、游離性強的特性，高度選擇性地(highly selective)殺死癌細胞，以達成有效殺死大量癌細胞並避免傷及周邊正常組織細胞的目的。
本研究使用釋出低能量貝他粒子及鄂惹電子之放射性核種，模擬其分布於細胞表面之情形，然後照射用於模擬細胞之組織等效比例計數器(Tissue Equivalent Proportional Counter, TEPC)，以研究放射免疫治療核種對細胞生物敏感區內之能量沈積的分布情形，並探討這些分布所引起的生物效應關係，以期許將來可作為輻射生物、輻射防護以及核醫治療上的評估參考。

六、參考文獻
1. Tien, H. F. Molecular Therapy in Hematologic
Malignancies. Formosan. J. Med. 2003; 7:212-221.
2. Hsieh, R. K. Molecular Targeted Therapy for Solid
Tumors. Formosan. J. Med. 2003; 7:222-226.
3. Tien, H. F. Molecular Therapy in Hematologic
Malignancies. Formosan. J. Med. 2003; 7:212-221.
4. N. Chawapun. Update on clinical radiobiology. Biomed
Imaging Interv J. 2006; 2(1):e22.
5. Rhonda Kalyn. Overview of targeted therapies in
Oncology. J Oncol Pharm Practice 2007; 13:199-205.
6. Silverstein, A. M. 1988. A history of immunology.
Academic Press, San Diego, California.
7. Bruland OS. Cancer therapy with radiolabeled
antibodies. An overview. Acta Oncol 1995; 34:1085-1094.
8. Jurcic JG, Scheinberg DA. Radioimmunotherapy of
hematological cancer: problems and progress. Clin
Cancer Res 1995; 1:1439-1446.
9. Kairemo KJ. Radioimmunotherapy of solid cancers: a
review. Acta Oncol 1996; 35:343-355.
10. Wilder RB, DeNardo GL, SJ. Radioimmunotherapy: recent
results and future directions. J Clin Oncol 1996;
14:1383-1400.
11. McDevitt, M. R., G. Sgouros, R. D. Finn, J. L. Humm,
J. G. Jurcic, S. M. Larson, and D. A. Scheinberg.
Radioimmunotherapy with alpha-emitting nuclides. Eur J
Nucl Med 1998; 25:1341.
12. Wessels BW, Rogus RD. Radionuclide selection and model
absorbed dose calculations for radiolabeled tumor
associated antibodies. Med Phys 1984; 11:638-645.
13. Richard A. Goldsby,Thomas J. Kindt, and Barbara A.
Osborne, Kuby Immunology. 4th ed., W.H. Freeman and
Company, New York, 2000.
14. Riley, M. B., & Byar, K. The rationale for and
background of radioimmuniotherapy : An emerging
therapy for B-cell non-Hodgkin’s lymphoma. Seminars
in Oncology Nursing 2004; 20(1):1-7.
15. Zimmer, A. M. Logistics of radioimmunotherapy with
yttrium 90 ibritumomab tiuxetan(zevalin). Seminars in
Nuclear Medicine 2004; 34(1 Sullp 1):14-19.
16. Kassis A. I., Adelstein S. J., Haydock C., Sastry K.
S. R., McElvany K. D. and Welch M. J. Lethality of
Auger electrons from the decay of bromine-77 in the
DNA of mammalian cells. Radiat. Res. 1982; 90:362-373
17. Sastry K. S. R. Biological effects of the Auger
emitter iodine-125: a review. Report No 1 of AAPM
Nuclear Medicine Task Group No 6. Med. Phys. 1992;
19:1361-1370
18. Ivan M. Roitt, Jonathan Brostoff, David K. Male,
Immunology. 5th ed., Mosby International Ltd., London,
1998.
19. Janeway, Charles A., et al., Immunobiology: The Immune
System in Health and Disease. 6th ed., Garland
Science, New York, 2005.
20. Kohler, G. and C. Milstein. Continuous cultures of
fused cells secreting antibody of predefined
specificity. Nature 1975; 256(5517): 495-497.
21. Maloney, D. G., T. M. Liles, D. K. Czerwinski, C.
Waldichuk, J. Rosenberg, A. Grillo-Lopez, and R. Levy.
Phase I clinical trial using escalating single-dose
infusion of chimeric anti-CD20 monoclonal antibody
(IDEC-C2B8) in patients with recurrent B-cell
lymphoma. Blood 1994; 84:2457.
22. Riethmuller, G., E. Schneider-Gadicke, G. Schlimok, W.
Schmiegel, R. Raab, K. Hoffken, R. Gruber, H.
Pichlmaier, H. Hirche, R. Pichlmayr, and et al.
Randomised trial of monoclonal antibody for adjuvant
therapy of resected Dukes’ C colorectal carcinoma.
German Cancer Aid 17-1A Study Group. Lancet 1994;
343:1177.
23. Handgretinger, R., K. Anderson, P. Lang, R. Dopfer, T.
Klingebiel, M. Schrappe, P. Reuland, S. D. Gillies, R.
A. Reisfeld, and D. Neithammer. A phase I study of
human/mouse chimeric antiganglioside GD2 antibody ch
14.18 in patients with neuroblastoma. Eur J Cancer
1995; 31A:261.
24. Burmeister J., Kota C. and Maughan R. L., Paired
miniature tissue-equivalent proportional counters for
dosimetry in high flux epithermal neutron capture
therapy beams, Nucl. Instrum. Methods Phys. Res. 1999;
A 422: 606-610.
25. International Commission on Radiation Units and
Measurements, Radiation Quantities and Units. Report
33, Washington, D.C., U.S.A., 1979.
26. International Commission on Radiation Units and
Measurements, Microdosimetry. Report 36, Bethesda,
Maryland, U.S.A., 1980.
27. H. Rossi, M. Zaider, Microdosimetry and its
applications, Springer, NY, U. S. A., 1996.
28. Unak, T., Potential Use of Radiolabeled Glucuronide
Prodrugs with Auger and/or Alpha Emitters in Combined
Chemo- and Radiotherapy of Cancer, Curr. Pharm. Des.
2000; 6:1127-1142.
29. Ftacnikova, S. and Bohm, R., Monte Carlo Calculations
of Energy Deposition on Cellular, Multicellular and
Organ Level for Auger Emitters, Radiat. Protect. Dos.
2000; 92(4):279-288.
30. Vandieren, E. B.; Vanlingen, A. P.; Roos, J. C. and
Teule, G. J. J., The relevance of uptake and
Intracellular Distribution for the Dosimetry of Auger
and Beta-Emitting Radionuclides in Micrometastases,
Radiat. Protect. Dos. 1994; 52(1-2):391-394.
31. K. S. R. Sastry, Biological effects of the Auger
emitter 125I: A review. Report No. 1 of AAPM Nuclear
Medicine Task Group No. 6. Med. Phys. 1992; 19: 1361-
1370.
32. K. S. R. Sastry and D. V. Rao, Dosimetry of low energy
electrons, in Physics of Nuclear Medicine: Recent
Advances, edited by D. V. Rao, R. Chandra, and M.
Graham (American Institute of Physics, New York,
1984), pp. 169-208.
33. Humm J. L., Howell R. W. and Rao D. V., Dosimetry of
Auger-electron-emitting radionuclides: report No 3 of
AAPM Nuclear Medicine Task Group No. 6. Med. Phys.
1994; 21: 1901-1915.
34. Hofer K. G. and Hughes W. L., Radiotoxicity of
intranuclear tritium, 125iodine and 131iodine. Radiat.
Res. 1971; 47: 94–109.
35. Burki H. J., Roots R., Feinendegen L. E. and Bond V.
P., Inactivation of mammalian cells after
disintegrations of 3H or 125I in cell DNA at -196 ℃.
Int. J. Radiat. Biol. 1973; 24: 363–75.
36. Chan P. C., Lisco E., Lisco H. and Adelstein S. J.,
The radiotoxicity of iodine-125 in mammalian cells: II
a comparative study on cell survival and cytogenetic
responses to 125IUdR;131IUdR and 3HTdR. Radiat. Res.
1976; 67: 332-343.
37. Adelstein S. J., The Auger process: a therapeutic
promise? Am. J. Roentgen. 1993; 160: 707-713.
38. Howell R. W., Radiation spectra for Auger-electron
emitting radionuclides: report No 2 of AAPM
NuclearMedicine Task Group No 6. Med. Phys. 1992; 19:
1371–1383.
39. Sastry K. S. R., Biological effects of the Auger
emitter iodine-125: a review. Report No 1 of AAPM
Nuclear Medicine Task Group No 6. Med. Phys. 1992; 19:
1361–1370.
40. ICRP. Radionuclide Transformations: Energy and
Intensity of Emissions., ICRP Publication 38. 1983.
41. L.A. Braby, G.W. Johnson and J. Barthe, Practical
considerations in the design and construction of
tissue-equivalent proportional counters. Radiation
Protection Dosimetry. 1995; Vol. 61, No. 4: 351-379.
42. International Commission on Radiation Units and
Measurements, Neutron dosimetry for biology and
medicine. Report 26, Washington, U.S.A., 1977.
43. International Commission on Radiation Units and
Measurements, Tissue substitutes in radiation
dosimetry and measurement. Report 44, Bethesda,
Maryland, U.S.A., 1989.
44. International Commission on Radiation Units and
Measurements, Determination of dose equivalents
resulting from external radiation sources. Report 39,
Bethesda, Maryland, U.S.A., 1985.
45. Caswell, R. S., Coyne, J. J. and Randolph, M. L.,
Kerma Factors for Neutron Energies Below 30 MeV.
Radiat. Res. 1980; 83: 217-254.
46. Caswell, R. S., Coyne, J. J. and Randolph, M. L.,
Kerma Factors of Elements and Compounds for Neutron
Energies Below 30 MeV. Int. J. Appl. Radiat. Isot.
1982; 33: 1227-1262.
47. A. J. Waker, Principles of experimental
microdosimetry. Radiation Protection Dosimetry. 1995;
Vol. 61, No. 4: 297-308.
48. S. Gerdung , P. Pihet, J. E. Grindborg et al.,
Operation and application of tissue-equivalent
proportional counters. Radiation Protection Dosimetry.
1995; Vol. 61, No. 4: 381-404.
49. Glenn F. Knoll, Radiation Detection and Measurement.
3rd ed. 2000: John Wiley & Sons, Inc.
50. J. Burmeister, C. Kota et al., Miniature tissue-
equivalent proportional counter for BNCT and BNCEFT
dosimetry, Med. Phys. 2001; 28 (9): 1911-1925.
51. James E. Turner, Atoms, Radiation, and Radiation
Prtotection. 2nd ed. 1995 by John Wiley & Sons, Inc.
52. Hall, Eric J. Radiobiology for the Radiologist, 5th
ed. 2000 by Lippincott Williams & Wilkins.
53. P. Pihet, H. G. Menzel et al., Biological weighting
function for RBE specification of neutron therapy
beams. Intercomparison of 9 European Centres. In:
Proc. 10th symp. on microdosimetry, Radiat. Prot.
Dosim. 1990; 31: 431-442.
54. S. Green, M. Gainey and C. Wojnecki, Determination of
an RBE for an Epithermal Neutron Beam for BNCT from
Microdosimetric Measurements, ISNCT8, LaJolla,
California, 1998.
55. T. Loncol, V. Cosgrove et al., Radiobiological
effectiveness of radiation beams with broad spectra:
microdosimetric analysis using biological weighting
functions, Radiat. Prot. Dosim. 1994, 52: 347-352.
56. G. Coutrakon, J. Cortese et al., Micordosimety
spectrum of the Loma Linda proton beam and relative
biological effectiveness comparisons, Med. Phys. 1997;
24: 1499-1506.
57. Range tables for using isotope:
http://physics.nist.gov/PhysRefData/Star/Text/ESTAR.html
58. Abrams PG, Fritzberg AR, editors. Radioimmunotherapy
of cancer, 2000 by Marcel Dekker, New York.
59. Bardies M, Chatal JF. Absorbed doses for internal
radiotherapy from 22 beta-emitting radionucides: beta
dosimetry of small spheres. Phys Med Biol 1994; 39:
961-981.
60. R. W. Hendricks, Space charge effects in proportional
counters. Rev. Sci. Instrum. 1969; 40: 1216–1223.