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1 Nucl Med Mol Imaging Vol. 40, No. 2, Apr 2006 방사성핵종을이용한치료에서흡수선량의평가 원자력의학원방사선의학연구센터핵의학연구실김경민 임상무 Internal Radiation Dosimetry in Radionuclide Therapy Kyeong Min Kim, Ph.D. and Sang Moo Lim, M.D. Nuclear Medicine Laboratory, Radiological and Medical Sciences Research Center, Korea Institute of Radiological and Medical Sciences, Seoul, Korea Radionuclide therapy has been continued for treatment of incurable diseases for past decades. Relevant evaluation of absorbed dose in radionuclide therapy is important to predict treatment output and essential for making treatment planning to prevent unexpected radiation toxicity. Many scientists in the field related with nuclear medicine have made effort to evolve concept and technique for internal radiation dosimetry. In this review, basic concept of internal radiation dosimetry is described and recent progress in method for dosimetry is introduced. (Nucl Med Mol Imaging 2006;40(2): ) Key Words : radionuclide therapy, internal radiation dosimetry 서론 방사성동위원소를직접이용하거나이를표지한방사성의약품 ( 이하방사성의약품 ) 을이용하여병소를치료하고자하는연구와노력들이오래전부터시도되고있다. 방사성동위원소를병소에집적시켜방사능을표적내에서방출시키는내부조사에의한치료법은외부조사에의한치료법에비해방사성의약품의생리적, 생화학적기능을이용하여표적부위에정상조직보다훨씬많은에너지를선택적으로조사할수있어서치료의효율적인면에서이론상으로유리하다. 개봉선원형태의방사성동위원소를이용하는내부조사치료는밀봉선원을이용하는외부조사에비해체내에서선원의분포와양을정확히평가하기어렵기때문에정확한체내흡수선량의평가와치료계획의수립이어렵다. 더욱이방사성의약품을이용한치료과정에서체내조직에축적되는방사성의약품에의한흡수선량은방사성의약품으로선택된 핵종은물론, 방사성의약품의화학적성질, 운반기전및체내대사와수행된치료방법에의해달라질수있다. 이러한흡수선량의정량적평가의어려움에도불구하고지난수십년간많은연구자들의노력으로방사성의약품을이용한많은치료법이개발되고소개되어실제임상에사용되고있으며, 이러한치료법의적합성과유효성을평가하기위한방법도함께개발되었다. 병소에특이적으로집적시킬수있는장점으로인해방사성의약품을이용한난치성질환의치료법의개발이근래에들어더욱주목을받고있다. 이논문에서는핵의학분야에서이용되는내부흡수선량평가방법에대해간략히설명하고, 최근활발히연구되고있는방사면역치료 (Radioimmunotherapy) 를중심으로한방사성의약품을이용한치료에서흡수선량평가를위해진행되고있는연구방법들을소개한다. 내부흡수선량의계산 Received: Accepted: Address for reprints: Kyeong Min Kim, Ph.D., Nuclear Medicine Laboratory, Radiological and Medical Sciences Research Center, Korea Institute of Radiological and Medical Sciences, #215-4, Gongneung-dong, Nowon-gu, Seoul , Korea Tel: , Fax: kmkim@kcch.re.kr 이연구는 2006 년과학기술부원자력연구개발사업 ( 방사성의약품이용치료및영상연구 ) 지원으로이루어졌음. 방사선의흡수선량을평가한다는것은방사선이매질을지날때구성원자의이온화또는여기화과정을통해매질의단위질량당흡수된에너지의양을의미한다. 방사선흡수선량의국제표준단위는 Gray (Gy) 로서, 1 Gy는매질 1 kg당 1 joule(j) 의에너지가흡수된양이다. 방사성의약품을이용한치료는방사선을방출하는방사성동위원소가체내에집적되어방사선을방출하게되므로내부선원에의한흡수선량의정량법이필요하다. 120

2 김경민외. 방사성핵종을이용한치료에서흡수선량의평가 내부방사선흡수선량평가 (Internal Radiation Dosimetry, 이하흡수선량평가 ) 란체내선원장기 (source organ) 로부터표적장기 (target organ) 로전달되는방사선의에너지흡수량을계산하는것을말한다. 이때선원장기와표적장기는같을수있고, 혹은한개이상일수도있다. 일반적으로하나의선원장기에서다른하나의표적장기로의흡수선량을계산하는과정은다음과같은 3단계의과정으로이루어진다. (1) 선원장기에집적된방사능의양과체류시간의결정 (2) 선원장기의방사능에의해방출된방사선에너지의총양의계산 (3) 선원장기에서방출된방사선에너지에대한표적장기의흡수분획을결정내부흡수선량을정확하게계산하기위해서는각단계마다많은번거롭고어려운과정이필요하지만, 실제사용에유용한흡수선량의계산에는선원장기및표적장기의방사선의평균에너지값을이용하여, 표적장기에전달되는평균적인흡수선량을추정한다. 1. MIRD공식의개념기존에많이행하여지고있는내부선량평가는 MIRD (Medical Internal Radiation Dosimetry) 라고알려진방법을이용한다. 1-10) 이방법은선원장기및표적장기를확인하여각각의경우에선원장기에서표적장기에전달되는특정방사선에의한흡수선량을선원장기내에집적된방사능의양 (cumulated dose) 과평형흡수선량계수 (equilibrium absorbed dose constant), 표적장기의무게, 흡수분획 (absorbed fraction) 의함수로표현하여계산한다. 특정표적장기에흡수된단위질량당방사선의흡수선량 (Gy) 을 MIRD 공식으로표현하면다음과같다. 으로한수학적팬텀을이용하여얻었다. 처음에 70kg의성인남자를기준하여수학적으로묘사한이후신체해부학적구조가다른성인여자와신생아로부터각연령대의신체및임신부의모델까지팬텀의수학적묘사가확장되어다양한신체조건에대한흡수분획계산에이용할수있게되었다. 평균흡수선량 D 을간단히표현하기위해서비흡수분획 (specific absorbed fraction, Φ) 과 S-value라는개념이도입되었다. 비흡수분획은위의흡수분획을표적장기의질량 ( m t ) 으로나눈값이다. Φ i (r t r s )= φ i(r t r s ) m t (2) 비흡수분획을이용하여단위집적방사능당평균흡수선량을의미하는 S-value 는다음과같이정의된다. S(r t r s )= 1 m t i φ i (r t r s )Δ i = i Φ i (r t r s )Δ i (3) S-value 는주어진방사성동위원소에대해선원장기와표적장기의기하학적구조와두장기간의매질의특성에따라결정되며, 이미핵의학분야에서사용되고있는많은방사성핵종에대해계산되어져있다. 따라서 MIRD 법에의한평균흡수선량은 S-value 를이용하여아래와같이단순화하여표현할수있다. D = Ã S(r t r s ) (4) 따라서표적장기의집적방사능 (cumulated activity) 과장기의질량, 그리고 S-value 를알면해당표적장기의총흡수선량 (Gy kg) 을계산할수있다. D(r t r s )=( Ã/m k ) i φ i (r t r s )Δ i (1) 식 (1) 에서 D(r t r s ) 은선원장기 ( r s ) 으로부터방출되는방사선에의한질량이 m k (kg) 인표적장기 ( r t ) 의평균흡수선량 (mean absorbed dose) 이고, Ã 는선원장기 (s) 에집적된방사능량, φ i (r t r s ) 은선원장기 (r s ) 에서방출되는 i 종류방사선에너지중표적장기 ( r t ) 에흡수되는에너지의비인흡수분획 (absorbed fraction), Δ i 는집적된방사성동위원소방사능의단위붕괴시방출되는특정방사선의수 ( N i ) 와그방사선의평균에너지 ( E i ) 의곱으로표현되는평형흡수선량계수이다. MIRD공식에서의이용되는흡수분획은성인남자를기준 2. MIRD법의활용선원장기내의방사능의양은시간에따라변하므로시간의변화에따른선원장기의방사능농도의변화곡선을얻어선원장기에집적된방사능을계산할수있다. A(t) 를 t 시간에서의순간방사능농도라고하면, 장기내집적된방사능의양은수학적으로선원장기내의처음방사능농도가 0 일때 (t = 0) 부터장기로부터완전히제거될때 (t = ) 까지의양으로아래의식으로표현할수있다. Ã= A(t)dt (5) 0 121

3 Kyeong Min Kim, et al. Internal Radiation Dosimetry in Radionuclide Therapy 식 (5) 를이용하여집적방사능을얻는것은때로는어려우므로방사성동위원소의물리적반감기 ( T p ) 에비해방사성의약품의체내섭취가순간적으로이루어지고생물학적배출이없다고가정할수있다면, 간편화된아래의수식으로장기에집적된방사능을계산할수있다. A(t)=A 0 e t/T p (6-1) Ã = A 0 0 e t/T p dt=1.44t p A 0 (6-2) 위의수식에서 A 0 는초기방사능이다. 그러나많은경우체내방사능은물리적반감기와더불어체내대사및순환에의한생물학적반감기 ( T b ) 의해배출되므로이들두반감기 T p 와 T b 를함께고려한유효반감기 ( T e ) 를사용하여집적방사능을계산한다. 1/T e =1/T p +1/T b (7-1) Ã =1.44T e A 0 (7-2) 위의두경우와달리장기내방사능의섭취가순간적이아니라섭취되는동안물리적붕괴를무시할수없을경우에는아래와같이계산을한다. A(t)=A 0 (1-e t/T u) (8-1) Ã =1.44A 0 T e (T ue /T u ) (8-2) 위의식에서 T u 는생물학적섭취반감기, T ue = T u T p /(T u + T p ), 그리고 T e 는앞의식 (7-1) 의유효반감기이다. 일반적으로흡수선량을계산할때표적장기의체류시간 (residence time, τ t ) 을많이이용한다. 이값은표적장기에집적된방사능 ( Ã) 을투여한방사능 ( A 0 ) 으로나누어 ( τ t = Ã/A 0 ) 하여얻을수있다. 실제흡수선량의계산에서는표적장기의시간-방사능곡선으로부터체류시간을얻고, 투여방사능량과해당 S-value 를이용하여표적장기의흡수선량 (Gy) 를계산한다. 흡수선량의계산은 MIRD 팜플렛의데이터를이용하여계산하거나, MIRDOSE 와같은프로그램들 11,12) 을사용하여계산할수있다. 최근에는체류시간의추정및 3차원영상을이용한흡수선량을사용자들이간편하게계산할수있도록도와주는프로그램들이활발히개발되고있다. 데이터획득및분석 흡수선량평가를위해서는일련의순차적인영상데이터를획득한다. 방사성동위원소를이용한치료로는알파선, 베타선등이이용될수있으나, 주로베타선을방출하는핵종이치료에많이이용된다. 베타선과감마선을동시에방출하는치료용핵종을사용하는경우 ( 예 : I-131) 치료와동시에핵의학영상을얻어체내의방사성의약품의분포와양을측정하여흡수선량을평가할수있다. 13) 이에반해핵의학영상에적합한감마선을방출하지않는베타선방사성핵종의경우 ( 예 : Y-90) 는적은양의핵의학영상진단용핵종 ( 예 : In-111) 으로추적자검사를시행한후흡수선량평가자료에의한치료를하거나핵의학영상진단용핵종을치료용핵종과동시에사용하여치료시의흡수선량을평가한다. 14) 골수의흡수선량을계산하기위해순차적으로일련의채혈을통해혈액의방사능농도도측정한다. 전신의방사능양을측정하기위해서이전에는전신계수기를사용하기도했으나, 근래에는감마카메라를이용하여전신평면영상을얻은후영상으로부터전신의방사능양을추정한다. 최근에들어서는 SPECT 나 PET과같은 3차원적인영상을이용하여단위조직당집적방사능의양을정확히추정하려는방향으로흡수선량평가법에관한연구들이활발히진행되고있다. 체내의흡수선량을정확하게평가하기위해서는앞서기술한바와같이선원및표적장기에방사능의양과체류시간등과같은양을정확히측정하는것이중요하며, 이를위해서는정량적인핵의학영상을얻은것이필요하다. 1. 정량적평면영상법감마카메라를이용하여정량적인평면영상을얻기위해전 (anterior) 후면 (posterior) 의평면영상 (planar image) 을동시에얻고이두영상으로부터관심영역의기하학적평균 (geometric mean) 값을얻는방법 (conjugate-view method) 이널리이용된다. 이때정량적정확도를높이기위해외부평면선원 ( 주로 Co-57) 을이용하여감마카메라만있는상태에서공백촬영 (blank scan) 을실시하고방사성의약품을체내에투여하기전에환자의투과촬영 (transmission scan) 을각각시행하여, 방사성의약품투여후방출촬영 (emission scan) 으로얻은평면영상에서의감쇠 (attenuation) 정도를보정한다. 평면영상의계수값을방사능의값으로변환하기위해서이미방사능의양을알고있는표준선원 (standard source) 을이용하여감마카메라의방사성-계수의상대적민감도를반영하는조정상수 (calibration factor, CF, μci/cps) 를구해평면영상으로부터얻은계수값에적용한다. 그리고 122

4 김경민외. 방사성핵종을이용한치료에서흡수선량의평가 선택적으로산란보정을통해획득된평면영상의질과정량적정확도를높일수도있다. 특히 I-131과같이높은에너지의산란된감마선이많이측정되는방사성핵종의영상을얻을경우는산란보정이강하게권고된다. 전 후면평면영상으로부터표적장기의방사능계수값을얻을때에는표적장기주변의배후방사능 (background activity) 의영향을보정하는것이필요하며, 아래의식을이용하여평면영상으로부터관심영역의정량적방사능 (Activity) 을측정할수있다. Activity = CF (C A-BKG A ) (C P -BKG p ) e - μ L/2 (9) 식 (9) 에서 C A 와 C P 는각각전면 (anterior) 과후면 (posterior) 평면영상에서관심영역의계수값 (cps, count per second), BKG A 와 BKG P 는각각전, 후면영상에서배후영역의계수값이다. 그리고 μ는선형감쇠계수 (linear attenuation coefficient) 이고 L은환자의신체두께 (cm) 이다. 이렇게얻은시간대별전, 후면의핵의학영상으로부터전신및표적장기의방사능양을측정한후집적방사능및체류시간을추정한다. 2. 정량적감마영상획득 흡수선량의평가를위해핵의학영상에이용되는핵종들중에서방사면역치료법에 I-131과 In-111등이많이이용된다. 이중 I-131 은이미수십년전부터핵의학영상에사용되어져온핵종으로, 베타선과감마선을동시에방출하므로베타선에의한치료효과를외부에서감마선을이용한핵의학영상을통해직접가시화하여평가할수있다. 그러나 I-131 은여러개의주에너지감마선의방출로인해깨끗한영상질을가진정량적인영상을얻기가어렵다. I-131 영상의질을높이고정량적정확도를높이기위해서고에너지 (high energy) 조준기 (collimator) 를사용하여영상을획득하지만, 많은양의산란성분과높은에너지를가진감마선의조준기의격벽투과 (septa penetration) 를효과적으로억제하기에는충분하지않다. Koral 등 15) 은초고에너지 (ultra high energy) 조준기를이용하여고에너지조준기에비해산란성분의대폭감소와향상된영상분해능의 I-131 영상을얻었다. 조준기를이용하여감마선산란성분을줄이고영상의질을개선할수있으나충분하지않다. 핵의학영상에서산란은영상의대조도를떨어뜨리기때문에영상을정량적, 정성적으로개선하기위해서는산란의보정이필요하다. 이미많은연구자들에의해 I-131의산란성분을제거하기위한여러방법들이개발되어활용되고있다 ) 영상획득시여러개 의에너지창 (energy window) 을열어얻은투사 (projection) 데이터를이용한방법과주 (main) 에너지창으로얻은투사데이터에서산란분포함수 (scatter distribution function) 를이용하여수학적으로산란성분을추정하여제거하는방법등이소개되었다. 이중임상현장에서는에너지창을이용하는방법중에서 3개의창을이용하여 3개의투사데이터를얻은후주에너지창에서얻은투사데이터로부터산란성분을제거하는상중에너지창 (triple energy window) 방법이많이사용된다. In-111 의경우 I-131 에비해낮은감마선에너지를방출하고, I-131 과마찬가지로복수의에너지창방법에의해산란성분을보정할수있다. 방사성동위원소치료시많은양의치료용방사성의약품을투여한후후향적 (retrospective) 으로흡수선량을평가하는경우가있다. 이러한경우투여직후체내에분포한방사성의약품의양과분포를감마카메라로측정할때측정기기의불응시간 (deadtime) 으로인해실제보다적게평가된다. 따라서고용량의방사성의약품을이용한치료시적절한흡수선량평가를위해서는측정과정에서불응시간에의한영향을보정해야한다. 불응시간에의한영상계수의영향을평가하기위해서는사전실험을통해장비의불응시간을측정한후이를이용할수도있고, 22) 환자영상획득시표준선원을영상의관심시야내에위치시킨후함께영상을얻어해당영상의불응시간에의한계수편차를보정할수도있다. 3. 환자별흡수선량평가 (patient specific dosimetry) 방사성동위원소를이용해치료를하기위해고용량 (high dose) 의방사능을투여하는경우가많다 ) 그리고치료의효과를높이기위해서는고용량의치료용방사성의약품을반복적으로투여하기도한다. 진단의경우와달리치료의목적으로방사성의약품을체내에투여하기위해서는고용량의방사성의약품이체내에투여되었을때방사성독성이나타나지않는범위내에서정상조직이견딜수있는최대량으로투여량이제한된다. 그러므로투여가능한방사능의양을미리추정하는치료계획이필요하다 ) 치료계획을위해서는적은양의방사성의약품을미리환자에투여하여흡수선량평가법으로전신의체류시간 ( T res ) 을추정한후, 미리몬테카를로시뮬레이션을이용하여얻은전신 S-value 와아래의공식을이용하여치료를위해필요한최대투여가능방사성의약품의양 (Therapeutic dose, D Therapy, mci) 을추정한다 30). D Therapy (mci)= Activity hr(mci hr) T res (hr) TBD(cGy) 75 cgy (10) 123

5 Kyeong Min Kim, et al. Internal Radiation Dosimetry in Radionuclide Therapy 위의식에서 TBD는기대되는전신의흡수선량 (total body dose) 로서보통 65cGy나 75cGy이고, Activity hr은 75cGy 의 TBD를전달하는데필요한양이다. Wahl 등 30) 은위의방법을제안하면서전신 S-value 를얻기위해몬테카를로시뮬레이션에서타원체로구성된인체모형을가정하였다. 최근에는환자개인의 CT나 MRI 등의 3차원해부학적영상과 SPECT 나 PET과같은 3차원적방사능의분포영상을몬테카를로시뮬레이션에이용하여화소 (voxel) 단위의 S-value 를구하고 3차원적인흡수선량의분포지도등을얻어환자개인의전신및장기별흡수선량을이전보다더욱정확하게계산할수있다 ) 4. 골수흡수선량평가 (Marrow Dosimetry) 골수는전신의방사성의약품치료시투여량제한장기이므로골수의흡수선량은특별히관리되어야한다. 치료용핵종을표지한항체 (antibody) 의비특이적골수집적에의한흡수선량의평가에는채혈데이터를이용한방법이일반적으로이용되고있다 ) 이방법 35) 은혈액내적색골수 (red marrow, RM) 의비율이 0.36이고, 골수내에서항체제거율이혈액에서와같으며, 골수내의항체분포가균일하다고가정하고계산을하다. 적색골수에흡수된선량 ( D RM ) 은다음의식으로표현할수있다. D RM =D RM RM +D RM RM (11) = Ã RM S(RM RM)+ Ã RB S(RM RM) 이식에서 RM은골수이외의전신을의미하고, S-value 들은이미알려진데이터를통해구할수있으며, 전신의집적방사능은전신영상혹은계수에서얻을수있다. 적색골수에집적된방사능을계산하기위해서는순차적인채혈로얻은일련의혈액의방사능을측정하여시간-방사능곡선을얻은후, 이중지수 (bi-exponential) 함수를이용하여혈액방사능의체류시간 ( τ blood ) 을구하고아래의모델공식 35) 을이용하여적색골수의체류시간 ( τ RM ) 을얻는다. τ = τ blood m,model m TB, patientl m TB,model 0.19 (1-hematocrit) (12) 위의식에서 m RM,model 은 MIRD 팬텀의적색골수모델의질량이고, m TB, patient 와 m TB,model 은각각환자와 MIRD 팬텀의전신체중을의미한다. 추정된적색골수의체류시간과투여치료방사능을이용하여적색골수에집적된방사능 ( Ã ) 을계산한다. 위의간편화된공식과일련의혈액방사능을이용하여골수의흡수선량을평가할수있으나림프종, 백혈병등과같 이골수내에암세포가침습한경우에는항체의특이적골수집적이클경우도있어혈액을이용한흡수선령평가가적절하지않을수도있다. 이러한경우핵의학적평면영상으로부터골수내의방사능을정량화하여흡수선량을평가할수도있고, 재현성도좋은것으로보고되었다 40,41). 그러나방사면역치료를위한방사성의약품투여영상에서는평면영상을이용한방법으로는골수의영역의방사능을정확히평가하는것이부적합할수도있어, SPECT/CT 에서얻은 SPECT 와 CT의영상을이용하여보다정확하게골수영영의방사능농도를얻어골수의흡수선량을평가할수있다 42). 5. 3차원영상을이용한종양의흡수선량평가흡수선량평가에감마카메라의평면영상을이용한방법이많이이용되고있으나, 3차원적인인체내기관이 2차원에중첩되어영상화되고 3차원적방사능의분포에따른감쇠와산란이 2차원적영상으로표현되는한계가있다. 기존의확립된 MIRD 공식을이용한흡수선량의계산법은선원장기로부터표적장기로의평균흡수선량을계산하기위해이미수학적팬텀으로부터얻은정해진 S-value 를이용한다. 이 S-value 는개별선원장기가균일하게분포된밀도를가지고있으며다른장기와결합되어있지않다고가정하고있으며, 표준인팬텀의장기크기와모양에의존한다. 선원장기에서방사선에너지는선원방사능의분포, 선원장기의크기와모양, 선원장기와표적장기간의기하학적관계등에영향을받는다. 저용량 (low dose) 의방사능이사용되는경우에는기존의표준인 (reference man) 의균일한장기모델을가정한흡수선량추정이그리문제가되지않으나, 치료목적을위한고선량의방사능을사용하는경우에는보다정확한선량계산이요구된다. 또한표준인팬텀의장기를이용하는경우에는종양과같은특정병소조직의위치나크기와모양을알수없어병소조직의치료를위한정확한선량계산이어렵고, 실제로체내장기의분포도사람마다다르고, 균일하지도않다. 환자의개인별정확한흡수선량평가에 3차원영상을이용하면유리하다. 즉, SPECT 나 PET과같은방사능분포와 CT나 MRI 와같은해부학적정보를이용하면국소별장기의흡수선량평가를보다정확하게할수있다 ) 특히최근에임상에도입되고있는 SPECT/CT 나 PET/CT 와같은영상장비는정확하게정합된 3차원적인방사능의분포와해부학적영상을함께얻을수있어개선된흡수선량평가에더욱유리하다. 3차원영상을이용하여흡수선량을평가하기위해서는 SPECT 를기존의평가법과같이순차적으로얻어흡수선량을평가하거나, 기존의평면영상법과 3차원영상을함께사용할수있다. Sjögreen 등 50) 과평면영상을이용한 124

6 김경민외. 방사성핵종을이용한치료에서흡수선량의평가 흡수선량평가에 CT영상에서얻은해부학적정보를결합함으로써국소별흡수선량평가를위한방법을제안하였다. 그리고 Koral 등 51) 은기종의평면영상과일회획득의 SPECT 영상을함께사용함으로써기존의방법에비해흡수선량평가의정확도를향상할수있음을보였다. 또한 SPECT 영상을이용할경우감마선의감쇠와산란의보정외에도, 단면영상재구성시적절한영상재구성방법의선택이요구된다. 그리고작은표적장기의흡수선량의평가를위해서는부분용적효과 (partial volume effect) 에대한고려도필요하다. 52) 앞서기술한바와같이 SPECT 나 PET과같은방사능분포와 CT나 MRI 와같은해부학적정보를환자별흡수선량의계산을계산하는데이용할수있다. 이러한과정은핵의학영상과해부학적영상의정확한분할 (segmentation) 과정합 (registration) 이필요하며, 몬테카를로시뮬레이션과같은컴퓨터를이용한계산과정이필요하다 ) 최근에향상된컴퓨터의성능과개선된계산방법등으로환자별흡수선량평가가보다활성화될것으로기대되고있다. 결 방사성의약품을이용한치료는난치성질환의극복을위한수단으로최근새로이주목을받고있다. 적절한방사성핵종의선택과이를표지한의약품의개발과적절하고유용한치료방법의개발및적용등은효율적인질환치료를위해필요하다. 방사성의약품을이용한치료의적합성과유효성의입증및효율적인치료계획을위해정확한흡수선량의평가가중요하다. 따라서앞으로더욱늘어나리라예상되는방사성의약품을이용한치료법의개발및활용을위해서흡수선량의평가법의개발및개선을위한많은관심과노력이요구된다. Reference 1. Loevinger R, Budinger TF, Watson EE. MIRD primer for absorbed dose calculation. New York: The Society of Nuclear Medicine; Macey DJ, williams LE, Breitz HB. Liu A, Johnson TK, Zanzonico PB. AAPM report No. 17: a primer for radioimmunotherapy and radionuclide therapy. American Association of Physicists in Medicine; Macey DJ, williams LE, Breitz HB. Liu A, Johnson TK, Zanzonico PB. AAPM report No. 17: a primer for radioimmunotherapy and radionuclide therapy. American Association of Physicists in Medicine; 김은실, 김종순, 김은희. 방사선안전관리. 고창순편저. 핵의학. 제 2 판. 서울 : 고려의학 ; p 임상무, 홍성운. 방사성의약품치료. 고창순편저. 핵의학. 제 2 판. 서울 : 고려의학 ; p 론 6. Zanzonico PB, Brill AB, Becker DV. Radiation Dosimetry. In: Wagner Jr HN, Szabo Z, Buchanan JW editors. Priciples of Nuclear Medicine. 2nd ed. Philadelphia: W.B.Saunders Company; p Internal radiation dosimetry. In: Cherry SR, Sorenson JA, Phelps ME. editors. Physics in Nuclear Medicine. 3rd ed. Philadelphia: Saunders; p Sgouros G. Dosimetry of internal emitters. J Nucl Med 2005;46: 18S-27S. 9. Siegel JA, Thomas SR, Stubbs JB, Stabin MG, Hays MT, Koral KF, et al. MIRD pamphlet no. 16: techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates. J Nucl Med 1999;40: 37S-61S. 10. Bolch WE, Bouchet LG, Robertson JS, Wessels BW, Siegel JA, Howell RW, et al. MIRD pamphlet No. 17: the dosimetry of nonuniform activity distributions--radionuclide S values at the voxel level. Medical Internal Radiation Dose Committee. J Nucl Med 1999;40:11S-36S. 11. Stabin MG. MIRDOSE: personal computer software for internal dose assessment in nuclear medicine. J Nucl Med 1996;37: Stabin MG, Sparks RB, Crowe E. OLINDA/EXM: the secondgeneration personal computer software for internal dose assessment in nuclear medicine. J Nucl Med 2005;46: Turner JH, Martindale AA, Boucek J, Claringbold PG, Leahy MF. 131 I-Anti CD20 radioimmunotherapy of relapsed or refractory non-hodgkins lymphoma: a phase II clinical trial of a nonmyeloablative dose regimen of chimeric rituximab radiolabeled in a hospital. Cancer Biother Radiopharm 2003;18: Wiseman GA, Kornmehl E, Leigh B, Erwin WD, Podoloff DA, Spies S, et al. Radiation dosimetry results and safety correlations from 90 Y-ibritumomab tiuxetan radioimmunotherapy for relapsed or refractory non-hodgkin's lymphoma: combined data from 4 clinical trials. J Nucl Med 2003;44: Dewaraja YK, Ljungberg M, Koral KF. Accuracy of 131 I tumor quantification in radioimmunotherapy using SPECT imaging with an ultra-high-energy collimator: Monte Carlo study. J Nucl Med 2000; 41: Delpon G, Ferrer L, Lenta C, Lisbona A, Buvat I, Bardies M. Comparison of four scatter correction methods for patient whole-body imaging during therapeutic trials with iodine-131. Cancer 2002 Feb 15;94: Zaidi H, Koral KF. Scatter modelling and compensation in emission tomography. Eur J Nucl Med Mol Imaging 2004;31: Leichner PK, Koral KF, Jaszczak RJ, Green AJ, Chen GT, Roeske JC. An overview of imaging techniques and physical aspects of treatment planning in radioimmunotherapy. Med Phys 1993;20: Dewaraja YK, Ljungberg M, Koral KF. Monte Carlo evaluation of object shape effects in iodine-131 SPET tumor activity quantification. Eur J Nucl Med 2001;28: Dewaraja YK, Ljungberg M, Koral KF. Characterization of scatter and penetration using Monte Carlo simulation in 131 I imaging. J Nucl Med 2000;41: Macey DJ, Grant EJ, Bayouth JE, Giap HB, Danna SJ, Sirisriro R, Podoloff DA. Improved conjugate view quantitation of I-131 by subtraction of scatter and septal penetration events with a triple energy window method. Med Phys 1995;22: Koral KF, Zasadny KR, Ackermann RJ, Ficaro EP. Deadtime correction for two multihead Anger cameras in 131 I dual-energywindow-acquisition mode. Med Phys 1998;25:

7 Kyeong Min Kim, et al. Internal Radiation Dosimetry in Radionuclide Therapy 23. Rajendran JG, Fisher DR, Gopal AK, Durack LD, Press OW, Eary JF. High-dose 131 I-tositumomab (anti-cd20) radioimmunotherapy for non-hodgkin's lymphoma: adjusting radiation absorbed dose to actual organ volumes. J Nucl Med 2004;45: Behr TM, Griesinger F, Riggert J, Gratz S, Behe M, Kaufmann CC, et al. High-dose myeloablative radioimmunotherapy of mantle cell non-hodgkin lymphoma with the iodine-131-labeled chimeric anti-cd20 antibody C2B8 and autologous stem cell support. Results of a pilot study. Cancer 2002;94: Menzel C, Grunwald F, Schomburg A, Palmedo H, Bender H, Spath G, et al. "High-dose" radioiodine therapy in advanced differentiated thyroid carcinoma. J Nucl Med 1996;37: Mayer A, Tsiompanou E, Flynn AA, Pedley RB, Dearling J, Boden R, et al. Higher dose and dose-rate in smaller tumors result in improved tumor control. Cancer Invest 2003;21: DeNardo SJ, Williams LE, Leigh BR, Wahl RL. Choosing an optimal radioimmunotherapy dose for clinical response. Cancer 2002;94: Erwin WD, Groch MW, Macey DJ, DeNardo GL, DeNardo SJ, Shen S. A radioimmunoimaging and MIRD dosimetry treatment planning program for radioimmunotherapy. Nucl Med Biol 1996;23: Zanzonico P, Sgouros G. Predicting myelotoxicity in radioimmunotherapy: what does dosimetry contribute? J Nucl Med 1997;38: Wahl RL, Kroll S, Zasadny KR. Patient-specific whole-body dosimetry: principles and a simplified method for clinical implementation. J Nucl Med 1998;39:14S-20S. 31. Furhang EE, Chui CS, Kolbert KS, Larson SM, Sgouros G. Implementation of a Monte Carlo dosimetry method for patientspecific internal emitter therapy. Med Phys 1997;24: Yoriyaz H, Stabin MG, dos Santos A. Monte Carlo MCNP-4Bbased absorbed dose distribution estimates for patient-specific dosimetry. J Nucl Med 2001;42: Furhang EE, Chui CS, Sgouros G. A Monte Carlo approach to patient-specific dosimetry. Med Phys 1996;23: Kolbert KS, Sgouros G, Scott AM, Bronstein JE, Malane RA, Zhang J, et al. Implementation and evaluation of patient-specific three-dimensional internal dosimetry. J Nucl Med 1997;38: Sgouros G. Bone marrow dosimetry for radioimmunotherapy: theoretical considerations. J Nucl Med 1993;34: Shen S, DeNardo GL, Sgouros G, O'Donnell RT, DeNardo SJ. Practical determination of patient-specific marrow dose using radioactivity concentration in blood and body. J Nucl Med 1999;40: Wessels BW, Bolch WE, Bouchet LG, Breitz HB, Denardo GL, Meredith RF, et al. Bone marrow dosimetry using blood-based models for radiolabeled antibody therapy: a multiinstitutional comparison. J Nucl Med 2004;45: Behr TM, Behe M, Sgouros G. Correlation of red marrow radiation dosimetry with myelotoxicity: empirical factors influencing the radiation-induced myelotoxicity of radiolabeled antibodies, fragments and peptides in pre-clinical and clinical settings. Cancer Biother Radiopharm 2002;17: Sgouros G, Stabin M, Erdi Y, Akabani G, Kwok C, Brill AB, et al. Red marrow dosimetry for radiolabeled antibodies that bind to marrow, bone, or blood components. Med Phys 2000;27: Siegel JA, Pawlyk DA, Lee RE, Sasso NL, Horowitz JA, Sharkey RM, et al. Tumor, red marrow, and organ dosimetry for 131 I-labeled anti-carcinoembryonic antigen monoclonal antibody. Cancer Res 1990;50:1039S-1042S. 41. Macey DJ, DeNardo SJ, DeNardo GL, DeNardo DA, Shen S. Estimation of radiation absorbed doses to the red marrow in radioimmunotherapy. Clin Nucl Med 1995;20: Boucek JA, Turner JH. Validation of prospective whole-body bone marrow dosimetry by SPECT/CT multimodality imaging in 131 I-anti-CD20 rituximab radioimmunotherapy of non-hodgkin's lymphoma. Eur J Nucl Med Mol Imaging 2005;32: Zanzonico PB, Bigler RE, Sgouros G, Strauss A. Quantitative SPECT in radiation dosimetry. Semin Nucl Med 1989;19: Sgouros G, Barest G, Thekkumthala J, Chui C, Mohan R, Bigler RE, et al. Treatment planning for internal radionuclide therapy: three-dimensional dosimetry for nonuniformly distributed radionuclides. J Nucl Med 1990;31: Sgouros G, Chiu S, Pentlow KS, Brewster LJ, Kalaigian H, Baldwin B, et al. Three-dimensional dosimetry for radioimmunotherapy treatment planning. J Nucl Med 1993;34: Koral KF, Lin S, Fessler JA, Kaminski MS, Wahl RL. Preliminary results from intensity-based CT-SPECT fusion in I-131 anti-b1 monoclonal-antibody therapy of lymphoma. Cancer 1997;80: Koral KF, Zasadny KR, Kessler ML, Luo JQ, Buchbinder SF, Kaminski MS, et al. CT-SPECT fusion plus conjugate views for determining dosimetry in iodine-131-monoclonal antibody therapy of lymphoma patients. J Nucl Med 1994; 35: Ljungberg M, Sjogreen K, Liu X, Frey E, Dewaraja Y, Strand SE. A 3-dimensional absorbed dose calculation method based on quantitative SPECT for radionuclide therapy: evaluation for 131 I using monte carlo simulation. J Nucl Med 2002;43: Sgouros G, Squeri S, Ballangrud AM, Kolbert KS, Teitcher JB, Panageas KS, et al. Patient-specific, 3-dimensional dosimetry in non-hodgkin's lymphoma patients treated with 131 I-anti-B1 antibody: assessment of tumor dose-response. J Nucl Med 2003;44: Sjogreen K, Ljungberg M, Strand SE. An activity quantification method based on registration of CT and whole-body scintillation camera images, with application to 131 I. J Nucl Med 2002;43: Koral KF, Dewaraja Y, Li J, Lin Q, Regan DD, Zasadny KR, et al. Update on hybrid conjugate-view SPECT tumor dosimetry and response in 131 I-tositumomab therapy of previously untreated lymphoma patients. J Nucl Med 2003; 44: Koral KF, Yendiki A, Lin Q, Dewaraja YK, Fessler JA. Determining total I-131 activity within a VoI using SPECT, a UHE collimator, OSEM, and a constant conversion factor. IEEE Trans Nucl Sci 2004;51: Tagesson M, Ljungberg M, Strand SE. A Monte-Carlo program converting activity distributions to absorbed dose distributions in a radionuclide treatment planning system. Acta Oncol 1996;35: Gardin I, Bouchet LG, Assie K, Caron J, Lisbona A, Ferrer L, et al. Voxeldoes: a computer program for 3-D dose calculation in therapeutic nuclear medicine. Cancer Biother Radiopharm 2003;18: Sjogreen K, Ljungberg M, Wingardh K, Minarik D, Strand SE. The LundADose method for planar image activity quantification and absorbed-dose assessment in radionuclide therapy. Cancer Biother Radiopharm 2005;20: Dewaraja YK, Wilderman SJ, Ljungberg M, Koral KF, Zasadny K, Kaminiski MS. Accurate dosimetry in 131 I radionuclide therapy using patient-specific, 3-dimensional methods for SPECT reconstruction and absorbed dose calculation. J Nucl Med 2005;46:

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<31312EB1E8B0E6B9CE2E687770> Nucl Med Mol Imaging Vol. 42, No. 2, Apr 2008 방사선내부흡수선량의의학적적용 한국원자력의학원방사선의학연구소분자영상연구부김경민 임상무 Medical Application of Radiation Internal Dosimetry Kyeong Min Kim, Ph.D., Sang Moo Lim, M.D., Ph.D. Molecular