Nuclear Medicine Therapy

Transcription

1 Radonuclde Therapy and osmetry n Nuclear Medcne George Sgouros, Ph.. Russell H. Morgan ept of Radology & Radologcal Scence Johns Hopkns Unversty, School of Medcne Baltmore M Nuclear Medcne Therapy number of hts Radonuclde Therapy * - humans year % osmetry: and osmetry *( radoodne therapy OR "radonuclde therapy" OR "sotope therapy" OR "radommunotherapy" OR "radolabeled antbody therapy" OR "radommunoconjugate therapy ) AN ( dosmetry OR absorbed dose ); lmt =humans Radoodne Therapy Thyrod CA Thyrod Treatment Plannng How much I-131? - Fed - Benua-Leeper (avod tocty) - Tumor absorbed dose (kll tumor) 1

2 Thyrod Treatment Plannng Benua-Leeper: Repeated 2 Gy to thesub-therapeutc blood (surrogate TXfor canmarrow) lead to loss of radoodne 4.4 GBq (12avdty mc) WB retenton at 48 h Identfy 2.96 GBq largest (8 mc) admnstered WB f lungsactvty are nvolved* that would be Tracer safestudy yet optmally therapeutc Collect and count blood samples rawng on clncal eperence, formulated constrants Integrate blood on admnstered tme-actvty curve actvty beta-partcle energy absorbed n blood Measure whole-body actvty (probe or magng) Actvty-based constrant oes not reflect total absorbed dose - rhtsh: faster WB clearance Related to dose-rate but only for fed anatomy Pedatrc patents? Based on clncal eperence Easy to mplement Has prevented lung tocty *Benua RS, *Rall Leeper JE, R. et al. Fronters J Cln Endocrnol Thyrodology Metab Nuclear Medcne osmetry Cumulated Actvty number of ds. energy released per ds. mass of target tssue fracton that s absorbed A ( t) A A ~ ~ A A f f f A eff e e eff t eff t à Tme (d) f eff A (t) ~ A A 2

3 Basc Prncples Energy released per decay MIR: Radonuclde ata and ecay Schemes energy released per ds. fracton that s absorbed mass of target tssue photons electrons total Basc Prncples Basc Prncples fracton that s absorbed t s mass of target tssue mass of target tssue 3

4 Absorbed Fracton Basc Prncples photons electrons/alphas t s M t t s 1 s s 1 t s = s s = 1 MIR: S-Factors New approach NURBS t s M t S, absorbed dose per unt cumulated actvty t = Ã s1 S(t s1) + Ã s2 S(t s2) +. Wesley Bolch, Ph epartment of Nuclear & Radologcal Engneerng rector, Advanced Laboratory for Radaton osmetry Studes (ALRAS) wbolch@ufl.edu 4

5 UF hybrd phantoms Newborn Male Newborn Female 1-year Male 1-year Female 5-year Male 5-year Female 1-year Male 1-year Female 15-year Male 15-year Female Adult Male Adult Female Phantom-based dosmetry Two Components Integral of tme-actvty curve - Imagng - Samplng - Clncal constrant - Actvty concentraton vs tme S-Factor - Phantom, radonuclde MC S(t s) 3- osmetry Patent-specfc - patent's anatomy (CT/MRI) - patent's actvty dstrbuton (SPECT/PET) Spatal dstrbuton of dose - non-unform actvty dstrbuton - absorbed dose "mages" - dose volume-hstograms 3-I System Input: Regstered anatomc & functonal mages Convert mages from a varety of sources nto a common data format. efne regons-of -nterest volumes by drawng contours. Select source and target volumes for dose calculaton. ( CT/MRI mages, SPECT/PET mages) Calculate absorbed dose to target from source volume. Create 3 dose dstrbuton maps. Generate mean dose, dosevolume hstograms and parametrc mages. Kolbert et al. JNM 97 5

6 3-I Functon Access Panel Impact of photon energy on dose dstrbuton I kev I kev I kev Kolbert et al. JNM 97 Furhang et al. Med Phys Internal osmetry (3-I) Patent-Specfc, 3- magng data Voel-based absorbed dose calculaton Output as mages, mean dose or VH Energy densty 3- Radobologcal osmetry (3-R) Patent-Specfc, 3- magng data Voel-based absorbed dose calculaton Output as mages, mean dose or VH Energy densty Radobologcal modelng Better predct response and tocty Prdeau et al. J Nucl Med 7 6

7 Radobologcal Modelng Spatal Actvty strbuton Bologcally Effectve ose (BE) BE jk jk jk 2 ln(2) jk te ln(2) ensty Unt densty sphere Equvalent Unform ose (EU) e e 2 EU 1 ln P e d : sngle ht cell kll : two ht cell kll : repar constant of tssue t e : effectve half lfe (found per voel) Prdeau et al. J Nucl Med 7 Actvty Actvty same total actvty as above = 1. Gy EU = 1. Gy EU recovers f spatally unform = 1. Gy EU =.693 Gy EU vares when dose s not unform Prdeau et al. J Nucl Med 7 Half-lfe strbuton Half-Lfe strbuton Non-Unform Clearance Lung Tssue Inner sphere at effectve clearance half-lfe of 4hrs Outer shell at effectve clearance half-lfe of 2hrs nsde = 1. Gy BE nsde = Gy outsde = 1. Gy BE outsde = Gy Tumor Inner sphere at effectve clearance half-lfe of 4hrs Outer shell at effectve clearance half-lfe of 2hrs nsde = 1. Gy BE nsde = 1.9 Gy outsde = 1. Gy BE outsde = Gy CT Non Unform ensty n Lungs SPECT Clncal Thyrod Case Eff. Half-lfe Non Unform Clearance Prdeau et al. J Nucl Med 7 Non Unform Actvty strbuton Prdeau et al. J Nucl Med 7 7

8 Clncal Thyrod Case.5.4 ose Volume Hstogram ose(gy) Tumor Lung Mean ose = 57.7 Gy 9.5 Gy Mean BE = 58.5 Gy 9.8 Gy EU = 25. Gy 8.3 Gy Tumor Lung Prdeau et al. J Nucl Med 7 IRT-XRT A equvalence A from XRT fractonated A from IRT over tme What about bologcal equvalence? Use BE tumor spne XRT IRT IRT BE XRT 1 BE / 1 1 / N / IRT 1 / N 1 1 / / Hobbs et al. SNM 8 1 Pnnacle vew of IRT-XRT 5 Indvdual kdneys absorbed dose of 9 Y-OTATOC Usng 86Y-OTATOC quanttatve magng and MIROSE3.1 for dosmetrc calculatons (assumng a standard kdney volume) Barone, et al. JNM 5 Kdney absorbed dose (mgy/mbq) Therapy plannng: actvtes delverng 27 Gy to the kdneys MALE FEMALE Tocty assessment Hobbs et al. SNM 8 osmetry # 32 UNIVERSITE CATHOQUE E LOUVAIN 8

9 Creatnne clearance loss/year (% baselne) osmetry # 33 Importance of organ volume n self rradaton Correlaton between kdney dose (Gy) and creatnne clearance loss/year (% baselne) N=18 Standard kdney volumes ose Standard volume (Gy) Creatnne clearance loss/year (% baselne) Barone, et al. JNM 5 Kdney volumes measured by CT corte (7%) R=.54 p= Kdney dose CT volume (Gy) UNIVERSITE CATHOQUE E LOUVAIN osmetry # 34 ose rate ose fractonaton LQ model BE = Bologc effectve dose BE= + / T repar /T effect ²/n Quadratc term Quadratc term Lnear term Quadratc term when the number of cycle or dose rate when the radaton dose In kdneys T/2 of NA repar: 2-3 h / s low: 2-3 Gy Barone, et al. JNM 5 UNIVERSITE CATHOQUE E LOUVAIN Correlaton between BE and creatnne clearance loss/year The Problem defned Creatnne clearance loss/year (% baselne) R=.93 p<.1 Calculate energy deposton densty (.e., absorbed dose) n a partcular organ or tumor volume Bologc Effectve ose (Gy) Barone R, Borson-Chazot F, Valkema R, et al. J Nucl Med. 25 Jan;46 Suppl 1:99S-16S osmetry # 35 UNIVERSITE CATHOQUE E LOUVAIN 9

10 The Problem defned Inde of response and tocty: absorbed dose, (,y,z) absorbed dose rate, R(,y,z) Radosenstvty, R(,y,z) prolferaton rate, P(,y,z) Crtcalty (mportance n lkely organ falure), C(,y,z) Response = F(,R,R,P,C); F? Acknowledgments MSKCC Katherne Kolbert El Furhang Steven Larson Rchard Robbns Hopkns Hong Song Andy Prdeau Rob Hobbs Paul Ladenson avd Loeb Rchard Wahl NIH O OE 1