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PurposeRadiation dose calculated on tumors for radiopharmaceutical therapy varies significantly from tumor to tumor and from patient to patient. Accurate estimation of radiation dose requires multiple time point measurements using radionuclide imaging modalities such as SPECT or PET. In this report, we show our technical development of reducing the number of scans needed for reasonable estimation of tumor and normal organ dose in our pretherapy imaging and dosimetry platform of 124 I-metaiodobenzylguanidine (MIBG) positron emission tomography/computed tomography (PET/CT) for 131 I-MIBG therapy of neuroblastoma.MethodsWe analyzed the simplest kinetic data, areas of two-time point data for five patients with neuroblastoma who underwent 3 or 4 times of 124 I-MIBG PET/CT scan prior to 131 I-MIBG therapy. The data for which we derived areas were percent of injected activity (%IA) and standardized uptake value of tumors. These areas were correlated with time-integrated activity coefficients (TIACs) from full data (3 or 4 time points). TIACs are direct correlates with radiation dose as long as the volume and the radionuclide are known.ResultsThe areas of %IAs between data obtained from all the two-time points with time points 1 and 2 (day 0 and day 1), time points 2 and 3 (day 1 and day 2), and time points 1 and 3 (day 0 and day 2) showed reasonable correlation (Pearson's correlation coefficient |r|>0.5) with not only tumor and organ TIACs but also tumor and organ absorbed doses. The tumor and organ doses calculated using %IA areas of time point 1 and time point 2 were our best fits at about 20% individual percent difference compared to doses calculated using 3 or 4 time points.ConclusionsWe could achieve reasonable accuracy of estimating tumor doses for subsequent radiopharmaceutical therapy using only the two-time point imaging sessions. Images obtained from these time points (within the 48-h after administration of radiopharmaceutical) were also viewed as useful for diagnostic reading. Although our analysis was specific to 124 I-MIBG PET/CT pretherapy imaging data for 131 I-MIBG therapy of neuroblastoma and the number of imaging datasets was not large, this feasible methodology would generally be applicable to other imaging and therapeutic radionuclides with an appropriate data analysis similar to our analysis to other imaging and therapeutic radiopharmaceuticals.

PurposeIodine-131-m-iodobenzylguanidine ([(131)I]mIBG)-targeted radionuclide therapy (TRT) is a standard treatment for recurrent or refractory neuroblastoma with response rates of 30-40 %. The aim of this study is to demonstrate patient-specific dosimetry using quantitative [(124)I]mIBG positron emission tomography/X-ray computed tomography (PET/CT) imaging with a GEometry ANd Tracking 4 (Geant4)-based Monte Carlo method for better treatment planning.ProceduresA Monte Carlo dosimetry method was developed using the Geant4 toolkit with voxelized anatomical geometry and source distribution as input. The presegmented hybrid computational human phantoms developed by the University of Florida and the National Cancer Institute (UF/NCI) were used as a surrogate to characterize the anatomy of a given patient. S values for I-131 were estimated by the phantoms coupled with Geant4 and compared with those estimated by OLINDA|EXM and MCNPX for the newborn model. To obtain patient-specific biodistribution of [(131)I]mIBG, a 10-year-old girl with relapsed neuroblastoma was imaged with [(124)I]mIBG PET/CT at four time points prior to the planned [(131)I]mIBG TRT. The organ- and tumor-absorbed doses of the clinical case were estimated with the Geant4 method using the modified UF/NCI 10-year-old phantom with tumors and the patient-specific residence time.ResultsFor the newborn model, the Geant4 S values were consistent with the MCNPX S values. The S value ratio of the Geant4 method to OLINDA|EXM ranged from 0.08 to 6.5 of all major organs. The [(131)I]mIBG residence time quantified from the pretherapy [(124)I]mIBG PET/CT imaging of the 10-year-old patient was mostly comparable to those previously reported. Organ-absorbed dose for the salivary glands was 98.0 Gy, heart wall 36.5 Gy, and liver 34.3 Gy, while tumor-absorbed dose ranged from 143.9 to 1,641.3 Gy in different sites.ConclusionsPatient-specific dosimetry for [(131)I]mIBG TRT was accomplished using pretherapy [(124)I]mIBG PET/CT imaging and a Geant4-based Monte Carlo dosimetry method. The Geant4 method with quantitative pretherapy imaging can provide dose estimates to normal organs and tumors with more realistic simulation geometry, and thus may improve treatment planning for [(131)I]mIBG TRT.

This thesis investigates the crystallographic structure, domain morphology and electrical properties of single crystalline epitaxial (001)-oriented perovskitic lead zirconate titanate, Pb(ZrxTi(1-X))O3, (PZT) thin films. The particular goal of the thesis was to study the domain evolution and ferroelastic domain switching in epitaxial (001) bilayered PZT heterostructures as a function of layer thickness. The films were fabricated by pulsed laser deposition. Firstly, single layered PZT films were fabricated to set a benchmark for the bilayer film studies and to gain fundamental understanding of the lattice dependence on thickness. Systematic x-ray diffraction studies provide direct evidence of the change in lattice tetragonality (or c/a ratio) as a function of thickness. Results confirm the film relaxes with increasing thickness where the degree of relaxation is commensurate with the thickness. As a consequence, domain formation varies as a function of thickness. Having set a benchmark and gained understanding of the structure of single-layer epitaxial PZT thin films, bilayered thin films consisting of a tetragonal PZT layer either 30 nm or 100 nm in thickness were deposited on a 100 nm thick rhombohedral PZT layer, which in turn was PbZr0.30Ti0.70O3 and PbZr0.55Ti0.45O3. The domain morphology of the tetragonal layer was found not only to change as a function of thickness but also had a domain state totally different than of a single layer of similar thickness. The domain structure changes from a fully a1/a2 domain to a three domain stress-free c/a1/c/a2 state in the 30 nm to 100 nm thick tetragonal PZT layer respectively. We show that the a-axis orientated domains are formed not simply due to the presence of a mechanical strain but also from an imposed electrostatic interaction between the ferroelectric layers due to the interlayer coupling. Finally, the ferroelectric and electromechancial properties were investigated. Polarization switching experiments confirm large polarization and enhanced piezoelectric coefficient attributed to the motion of nanoscale ferroelastic domains. Piezoresponse force microscopy images also demonstrate gross movement for the ferroelastic domains under local bias. The results presented here thus provide fundamental insight into domain-engineered ferroelectric thin film devices and furthermore, report a practical approach to achieve thin films with giant piezoelectric coefficient without the use of complicated fabrication method