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1 Special Issue Nuclear Medicine in Oncology Chang Woon Choi, M.D. Department of Nuclear Medicine Korea Institute of Radiological and Medical Science cwchoi@kcch.re.kr Abstract Nuclear oncolgy is important in the diagnosis, staging, and long - term surveillance of a number of cancers. Over the past 10 years there has been an explosion of new radioisotopic tracers aimed at detecting, staging and eventually treating tumors. Clinicians and oncologists can now use specific radiolabeled metabolic tracers, monoclonal antibodies, and molecular probes based on the sequencing of the human genome. The current applications of positron emission tomography (PET) in oncology have included characterizing tumor lesions, differentiating recurrent disease from treatment effects, staging tumors, evaluating the extent of disease, and monitoring therapy. The future developments in medicine may use the unique capabilities of PET not only in diagnostic imaging but also in molecular medicine and genetics. Radioimmunoscintigraphy is a technique which uses radiolabeled antibodies to visualize tumors, taking advantage of antigens preferentially expressed by malignant tissue. However, the implementation of radiolabeled antibodies as magic bullets for detection and treatment of diseases such as cancer has required addressing several shortcomings of murine monoclonal antibodies. Genetic engineering provides a powerful approach for redesigning antibodies for use in oncologic applications in vivo. Recently, noninvasive molecular imaging has been developed. Most current molecular imaging strategies are indirect and involve the coupling of a reporter gene with a complementary reporter probe. Imaging the level of probe accumulation provides indirect information related to the level of reporter gene expression. In this article, the author discuss the current status of PET, radioimmunoscintigraphy, gene imaging and receptor imaging with a brief review on nuclear oncology. Keywords : Nuclear oncoloy; PET; Radioimmunoscintigraphy; Gene imaging 186

2 99m Tc 131 I 201 Tl 67 Ga 57 Co, 111 In bleomycin 18 F - FU 18 F cisplatin 131 I - MIBG 131 I 18 F - FDG somatostatin - receptor 18 F - estradiol 187

3 Special Issue FDG - PET.. 188

4 MRI FDG - PET, FET - PET. MRI (fluorodeoxyglucose: FDG) (fluoroethyltyrosine: FET).. 189

5 특집(최창운)Q :1PM 페이지190 Special Issue 핵의학의 최신지견 합을 통해서 리간드와의 결합력을 증가시킨 수용체를 개 발하기가 용이하나 면역체계에 인지되어서 면역반응을 유발하는 단점이 있다. 최근에 핵의학기법을 이용하여 비침습적인 방법으로 유전자의 발현을 평가하는 기법 중에서 가장 연구가 많이 되어있는 분야는 herpes simplex virus type 1 thymidine kinase (HSV1 - tk)를 reporter gene으로 하는 방 법이다. HSV1 - tk 유전자는 유전자 치료시 치료유전자 로서 종양 특이적으로 HSV1 - tk 유전자를 발현시키고 Ganciclovir(GCV)를 처리함으로써 종양특이적인 치료 를 실시할 목적으로 연구 개발되어 왔다. Tjuvajev(28 30) 등이 HSV1 - tk와 이 유전자 산물인 바이러스의 티 민 키나아제(thymidine kinase)에 특이적인 방사성 동 위원소가 표지된 핵산유도체를 이용하여 유전자가 발현 되는 세포에 기질의 인산화 과정에 의해서 선택적으로 포 획되어 집적되는 기전을 이용하는 방법을 보고하였다. 1995년에 Tjuvajev(29) 등은 방사성 동위원소 표지 핵산 유도체로서 GCV, 5 - iodo deoxyuridine(iudr), and 5 - iodo fluoro deoxy - β- D - arabi- 그림 3. Herpes simplex virus type 1 thymidine kinase(hsv1 tk) 유전자 영상. HSV1 - tk 유전자가 이입된 간암 세 포(MCA - tk) 종괴를 가진 백서모델에서 123I 표지 iodovinyldeoxyuridine(ivdu) 주사 후 2시간과 24시간 에 감마카메라 영상에서 우측 대퇴부에 섭취가 증가 된 종양이 관찰된다(화살표). nofuranosyl uracil(fiau)를 이용하여 비침습적인 유전 자 발현의 영상이 가능함을 보고하였다. Gambhir 등은 씬 높은 농도로 발현되고 있으며, 이에 대한 항체를 방사성 임상에서 사용하는 감마카메라와 SPECT를 이용하여 동위원소로 표지하여 암을 진단하고 치료하려는 연구가 진 HSV tk 유전자 발현을 영상화 하였다(31). 이러한 행되어 왔다. 이러한 종양관련 항원에 대한 항체를 만들고, 연구결과들로 볼 때 PET/HSV tk 영상화 기법은 방사성 동위원소 표지한 항체를 인체에 주입하면 이론적으 종양에 대한 임상에서 유전자 치료시 치료유전자의 이입 로 특이적으로 종양에 섭취되어 종양을 영상화할 수 있고 성공 여부 및 유전자의 발현을 평가할 수 있는 방법으로 이 검사법을 방사면역신티그라피(radioimunoscintigra- 기대된다. phy)라고 하며, 섭취가 높은 경우 다량의 치료용 방사성 동위원소를 표지한 항체를 투여하여 치료할 수 있으며 방 항체영상 : 방사면역신티그라피 사면역치료(radioimmunotherapy)라 한다. 종양관련 항원은 태아성 암항원(oncofetal antigen), 종양관련 항원은 각종 악성 종양에서 정상조직보다 훨 190 종양 핵의학 분화 및 조직특이성 항원, 성장인자 수용체 및 암 유전자

6 191

7 Special Issue 131 I - MIBG 111 In - Pentreotide Pheochromocytoma 86% 88% Neuroblastoma 91% 89% Paragangliomas 52% 100% Carcinoid 70% 96% 192

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9 Special Issue sion tomography. J Cereb Blood Flow Metab 1989 ; 9 : Willemsen ATM, van Waarde A, Paans AMJ, Pruim J, Luurtsema G, Vaalburg W, et al. In vivo protein synthesis rate determination in primary or recurrent brain tumors using L - [1-11C] - tyrosine and PET. J Nucl Med 1995 ; 36 : Rasey JS, Grierson JR, Wiens LW, Kolb PD, Schwartz JL. Validation of FLT uptake as a measure of thymidine kinase - 1 activity in A549 carcinoma cells. J Nucl Med 2002 ; 43 : Buck AK, Schirrmeister H, Hetzel M, Von Der Heide M, Halter G, Neumaier B, et al. 3 - deoxy [ 18 F]fluorothymidine - positron emission tomography for noninvasive assessment of proliferation in pulmonary nodules. Cancer Res 2002 ; 62(12) : Mier W, Haberkorn U, Eisenhut M. [ 18 F]FLT; portrait of a prolferation marker. Eur J Nucl Med 2002 ; 29 : PET ; 31 : PET ; 31 : PET ; 31 : PET ; 31 : PET ; 31 : PET ; 31 : FDG - PET ; 31 : FDG - PET ; 31 : FDG - PET ; 31 : PET ; 31 : PET/CT ; 31 : Tjuvajev JG, Avril N, Oku T, Sasajima T, Miyagawa T, Blasberg R, et al. Imaging herpes virus thymidine kinase gene transfer and expression by positron emission tomography. Cancer Res 1998 ; 58(19) : Tjuvajev JG, Finn R, Watanabe K, Joshi R, Oku T, Blasberg RG, et al. Noninvasive imaging of herpes virus thymidine kinase gene transfer and expression: a potential method for monitoring clinical gene therapy. Cancer Res 1996 ; 56(18) : Tjuvajev JG, Stockhammer G, Desai R, Uehara H, Watanabe K, Blasberg RG, et al. Imaging the expression of transfected genes in vivo. Cancer Res 1995 ; 55(24) : Gambhir SS, Barrio JR, Wu L, Iyer M, Namavari M, Herschman HR, et al. Imaging of adenoviral - directed herpes simplex virus type 1 thymidine kinase reporter gene expression in mice with radiolabeled ganciclovir. J Nucl Med 1998 ; 39 : Choi CW, Lang L, Lee JT, Webber KO, Yoo TM, Pastan I, et al. Biodistribution of 18 F - and 125 I - labeled anti - Tac disulfide - stabilized Fv fragments in nude mice with interleukin 2 alpha receptor - positive tumor xenografts. Cancer Res 1995 ; 55(22) : Yoo TM, Chang HK, Choi CW, Webber KO, Le N, Paik CH, et al. Technetium - 99m labeling and biodistribution of anti - TAC disulfide - stabilized Fv fragment. J Nucl Med 1997 ; 38 : Wu AM, Yazaki PJ. Designer genes: recombinant antibody fragments for biological imaging. Q J Nucl Med 2000 ; 44 : Sergides IG, Austin RC, Winslet MC. Radioimmunodetection: technical problems and methods of improvement. Eur J 194

10 Surg Oncol 1999 ; 25 : Kalofonos HP, Karamouzis MV, Epenetos AA. Radioimmunoscintigraphy in patients with ovarian cancer. Acta Oncol 2001 ; 40 : Berglund AS, Hulthen UL, Manhem P, Thorsson O, Wollmer P, Tornquist C. Metaiodobenzylguanidine (MIBG) scintigraphy and computed tomography (CT) in clinical practice. Primary and secondary evaluation for localization of phaeochromocytomas. J Intern Med 2001 ; 249 : Sisson JC, Shulkin BL. Nuclear medicine imaging of pheochromocytoma and neuroblastoma. Q J Nucl Med 1999 ; 43 : Sisson JC. Radiopharmaceutical treatment of pheochromocytomas. Ann N Y Acad Sci 2002 ; 970 : Bombardieri E, Maccauro M, De Deckere E, Savelli G, Chiti A. Nuclear medicine imaging of neuroendocrine tumours. Ann Oncol 2001 ; 12(Suppl 2) : S Signore A, Annovazzi A, Chianelli M, Corsetti F, Van de Wiele C, Watherhouse RN. Peptide radiopharmaceuticals for diagnosis and therapy. Eur J Nucl Med 2001 ; 28 : Behr TM, Gotthardt M, Barth A, Behe M. Imaging tumors with peptide - based radioligands. Q J Nucl Med 2001 ; 45 : Jonson SD, Welch MJ. PET imaging of breast cancer with fluorine - 18 radiolabeled estrogens and progestins. Q J Nucl Med 1998 ; 42(1) : ,,,,,. I estradiol ; 62 :

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김범수 Analysis of Outcomes after Resection of Sarcomatous Hepatocellular Carcinoma Purpose: Sarcomatous hepatocellular carcinoma (HCC) is rare. Therefore, the clinicopathologic characteristics and prognosis