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Voxel-based dosimetry of iron oxide nanoparticles based 177Lu-labeled folate conjugates targeted SPECT/CT imaging of mice : SPECT/CT를 이용한 생쥐에서 177Lu 표지 산화철 나노입자 기반 엽산 복합체의 복셀 기반 피폭선량 연구

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dc.contributor.advisor이 동수-
dc.contributor.author아룬-
dc.date.accessioned2018-11-12T01:01:39Z-
dc.date.available2020-10-06T07:17:43Z-
dc.date.issued2018-08-
dc.identifier.other000000151962-
dc.identifier.urihttps://hdl.handle.net/10371/143333-
dc.description학위논문 (박사)-- 서울대학교 대학원 : 의과대학 의학과, 2018. 8. 이 동수.-
dc.description.abstractPeptide-receptor radionuclide therapy (PRRT) has gained increasing importance for the treatment of various cancers including lymphoma, glioblastoma, neuroendocrine tumors and prostate cancer. The effectiveness of targeted radionuclide therapy (TRT) depends primarily on the absorbed dose rate and the total absorbed dose delivered to the tumor and to normal tissues. Hence, the absorbed dose must be determined as accurately as possible to obtain appropriate absorbed dose response–effect relationships. Due to the various limitations associated with organ-based dosimetry performed by MIRD schema, the voxel-based dosimetry has become essential for the assessment of more accurate absorbed dose.

The folate receptor (FR) has been identified as a target associated with varieties of tumors including ovarian and cervical carcinoma. Therefore, several folic acid conjugates using diagnostic and therapeutic radionuclides have been developed for targeted imaging and therapy. However, the therapeutic concept with radiolabeled folate conjugates has not been applied yet for clinical application due to higher renal absorbed dose caused by increased uptake in kidneys. To overcome these challenges, we prepared iron oxide nanoparticle (IONPs) based radiolabeled folate conjugate (177Lu-IONPs-Folate) and performed voxel-based dosimetry using SPECT/CT imaging of normal mice. In this thesis, we first performed voxel-based dosimetry in normal mice from whole-body 18F-fluorodeoxyglucose (18F-FDG) PET/CT imaging to evaluate the feasibility and reliability of image-based preclinical dosimetry using GATE MC toolkit. Secondly, we evaluated system performance and quantitative accuracy of NanoSPECT/CT scanner for 177Lu radioisotope using point source and uniform phantom studies. Finally, we estimated the absorbed doses at voxel-level using GATE MC from the SPECT/CT images of normal mice performed with 177Lu-Folate, 177Lu-IONPs and 177Lu-IONPs-Folate. We also calculated organ-based absorbed dose in the given organs due to all three radiotracers using MIRD schema.

MC simulation considers the true activity distribution and tissue heterogeneity during whole-body absorbed dose estimation at voxel-level. Therefore, the voxel-based absorbed dose estimated in the organs of mice from 18F-FDG PET would be more accurate. The results obtained from measured performance parameters were convincing to conduct preclinical SPECT/CT imaging. We found that the absorbed dose to the kidneys was significantly decreased when Iron-oxide nanoparticle based 177Lu-lableled folate conjugate (177Lu-IONPs-Folate) was used compared to 177Lu-Folate.

In conclusion, the absorbed dose values in the organs obtained at voxel-level using individualized activity and media distributions would be more accurate. This method can be used for personalized dosimetry in TRT to estimate maximum tolerated activity for therapy planning.
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dc.description.tableofcontentsAbstract ........................................................................................ i

Contents ………………………………………………………………… iii

List of Figures …………………………………………………………vi

List of Tables.............................................................................. ix



General Introduction ……………………………………………………1

Chapter 1. Feasibility and reliability of GATE MC for

Preclinical voxel-based dosimetry .............................................5

1.1. Background ...................................................................5

1.2. Materials and Methods .................................................7

1.2.1. Animal reparation 7

1.2.2. PET/CT acquisition 7

1.2.3. Organ mass estimation and image-based

biodistribution 7

1.2.4. GATE MC simulation 9

1.2.5. Voxel-based dosimetry method 10

1.2.6. Organ-based dosimetry method 11

1.3. Results.........................................................................12

1.3.1 PET Image-based biodistribution 12

1.3.2 Energy deposition and dose rate 12

1.3.3 Voxel-based absorbed dose 14

1.3.4 Organ-based absorbed dose 14

1.3.5 Voxel-based vs. organ-based absorbed dose 15

1.4. Discussion .................................................................. 17



Chapter 2. Performance Evaluation of NanoSPECT/CT

Scanner for 177Lu imaging .....................................................19

2.1. Background …………………………………………………19

2.2. Materials and Methods ……………………………………21

2.2.1. NanoSPECT/CT system 21

2.2.2. Point source and uniform phantom acquisition 21

2.2.3. Adding uniform background to point source data 23

2.2.4. Image reconstruction 23

2.2.5. System performance evaluation 24

2.3. Results 29

2.3.1. Recovery coefficient and uniformity 29

2.3.2. Spatial resolution 31

2.3.3. System sensitivity 32

2.3.4. Calibration factor 34

2.4. Discussion………………………………………………… 35



Chapter 3. Voxel-based dosimetry of 177Lu-labeled

folate conjugates targeted SPECT/CT imaging of mice……… 36

3.1. Background..................................................................36

3.2. Materials and Methods…………………………………… 38

3.2.1. Synthesis of 177Lu-labeled folate conjugates 38

3.2.2. Animal preparation 40

3.2.3. 177Lu-SPECT/CT Imaging 40

3.2.4. Image reconstruction 41

3.2.5. SPECT image-based biodistribution of

radiotracers 41

3.2.6. GATE MC simulation set up 43

3.2.7. Voxel-based dosimetry method 43

3.2.8. Organ-based dosimetry method 44

3.3. Results…………… …………………………………………45

3.3.1. SPECT image-based biodistribution 45

3.3.2. Energy deposition and dose rate 46

3.3.3. Voxel-based absorbed dose 48

3.3.4. Organ-based absorbed dose 51

3.3.5. Discussion ................................................................53

General Discussion and Conclusion ………………………………56

References………………………………………………………………59

Abstract in Korean…………………………………………………… 66
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dc.language.isoen-
dc.publisher서울대학교 대학원-
dc.subject.ddc610-
dc.titleVoxel-based dosimetry of iron oxide nanoparticles based 177Lu-labeled folate conjugates targeted SPECT/CT imaging of mice-
dc.title.alternativeSPECT/CT를 이용한 생쥐에서 177Lu 표지 산화철 나노입자 기반 엽산 복합체의 복셀 기반 피폭선량 연구-
dc.typeThesis-
dc.description.degreeDoctor-
dc.contributor.affiliation의과대학 의학과-
dc.date.awarded2018-08-
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