Yujin Qi

Synthesis, Biodistribution, and Microsingle Photon Emission Computed Tomography (SPECT) Imaging Study of Technetium-99m Labeled PEGylated Dendrimer Poly(amidoamine) (PAMAM)-Folic Acid Conjugates

Three conjugates based on dendrimer PAMAM generation five were synthesized and radiolabeled successfully. To investigate their tumor targeting, the in vitro and in vivo stability, cell uptake, in vivo biodistribution, and micro-SPECT imaging were evaluated, respectively. The conjugate of (99m)Tc labeled PEGylated dendrimer PAMAM folic acid conjugate ((99m)Tc-G5-Ac-pegFA-DTPA) shows much higher uptake in KB cancer cells and accumulated more in the tumor area than that of the other two conjugates. The uptake in KB cells depends on the incubation time. The results of in vivo biodistribution agree with the data obtained from micro-SPECT imaging. These studies show that PEGylation of PAMAM dendrimer folic acid conjugate improves the tumor targeting. Folate-conjugated dendrimer maybe developed to be potential radiopharmaceuticals and targeted drug delivery systems.

Radiosynthesis and micro-SPECT imaging of 99mTc-dendrimer poly(amido)-amine folic acid conjugate

Acetylated (Ac) dendrimer poly(amido)-amine (PAMAM) generation 5 (G5) reacted with folic acid (FA), followed by reacting with 2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetria minepentaacetic acid (1B4M DTPA) to form the conjugate of Ac-G5-FA-1B4M DTPA which was further radiolabeled with (99m)Tc. The radiochemical yield is up to 98.9% with excellent in vitro/in vivo stability, rapid blood clearance and certain tumor accumulation which was further confirmed by micro-SPECT imaging study.

BrachyView: Proof-of-principle of a novel in-body gamma camera for low dose-rate prostate brachytherapy

PURPOSE The conformity of the achieved dose distribution to the treatment plan strongly correlates with the accuracy of seed implantation in a prostate brachytherapy treatment procedure. Incorrect seed placement leads to both short and long term complications, including urethral and rectal toxicity. The authors present BrachyView, a novel concept of a fast intraoperative treatment planning system, to provide real-time seed placement information based on in-body gamma camera data. BrachyView combines the high spatial resolution of a pixellated silicon detector (Medipix2) with the volumetric information acquired by a transrectal ultrasound (TRUS). The two systems will be embedded in the same probe so as to provide anatomically correct seed positions for intraoperative planning and postimplant dosimetry. Dosimetric calculations are based on the TG-43 method using the real position of the seeds. The purpose of this paper is to demonstrate the feasibility of BrachyView using the Medipix2 pixel detector and a pinhole collimator to reconstruct the real-time 3D position of low dose-rate brachytherapy seeds in a phantom. METHODS BrachyView incorporates three Medipix2 detectors coupled to a multipinhole collimator. Three-dimensionally triangulated seed positions from multiple planar images are used to determine the seed placement in a PMMA prostate phantom in real time. MATLAB codes were used to test the reconstruction method and to optimize the device geometry. RESULTS The results presented in this paper show a 3D position reconstruction accuracy of the seed in the range of 0.5-3 mm for a 10-60 mm seed-to-detector distance interval (Z direction), respectively. The BrachyView system also demonstrates a spatial resolution of 0.25 mm in the XY plane for sources at 10 mm distance from Medipix2 detector plane, comparable to the theoretical value calculated for an equivalent gamma camera arrangement. The authors successfully demonstrated the capability of BrachyView for real-time imaging (using a 3 s data acquisition time) of different brachytherapy seed configurations (with an activity of 0.05 U) throughout a 60 × 60 × 60 mm(3) Perspex prostate phantom. CONCLUSIONS The newly developed miniature gamma camera component of BrachyView, with its high spatial resolution and real time capability, allows accurate 3D localization of seeds in a prostate phantom. Combination of the gamma camera with TRUS in a single probe will complete the BrachyView system.

Preliminary biological evaluation of 125I-labeled anti-carbonic anhydrase IX monoclonal antibody in the mice bearing HT-29 tumors

ObjectiveTo evaluate 125I-labeled anti-carbonic anhydrase IX monoclonal antibody (125I-MAb) as a novel single-photon emission computed tomography tracer for imaging carbonic anhydrase IX in the mice bearing HT-29 tumors. MethodsAnti-carbonic anhydrase IX monoclonal antibody was labeled with iodine-125 by the iodogen method. The radiochemical purity of 125I-MAb was measured by radio-thin-layer chromatography. The in-vitro stability of 125I-MAb was determined in PBS (0.05 mol/l, pH 7.4) or new-born calf serum at 37°C, and analyzed by radio-thin-layer chromatography. A biodistribution study and planar imaging were carried out in the mice bearing HT-29 tumors. The expression of CA IX in HT-29 tumors was analyzed by immunohistochemistry. Results125I-MAb was obtained with a radiolabeling efficiency of 98%, and showed high stability in PBS and new-born calf serum. Furthermore, the biodistribution study showed specific tumor uptake in the mice bearing HT-29 tumors, and planar imaging with 125I-MAb 48 h post injection showed a high concentration of radioactivity in tumors and a much decreased concentration in tumors in the blocking group. An immunohistochemical analysis showed the expression of CA IX in HT-29 tumors. ConclusionThe preliminary biodistribution study and results from planar imaging showed the potential of 125I-MAb as an agent for tumor diagnosis and encouraged further investigation.

Radiolabeling of RGD peptide and preliminary biological evaluation in mice bearing U87MG tumors.

2-[(18)F]Fluoroethyl azide ([(18)F]FEA) and terminal alkynyl modified propioloyl RGDfK were selected in this study. [(18)F]FEA was prepared by nucleophilic radiofluorination of 2-azidoethyl 4-toluenesulfonate with radiochemical yield of 71 ± 4% (n = 5, decay-corrected). We assessed the various conditions of the CuAAC reaction between [(18)F]FEA and propioloyl RGDfK, which included peptide concentration, reaction time, temperature and catalyst dosage. The (18)F-labeled-RGD peptide ([(18)F]F-RGDfK) could be obtained in 60 min by a two-step radiochemical synthesis route, with total radiochemical yield of 60 ± 2% (n = 3, decay-corrected) through click chemistry. [(18)F]F-RGDfK showed high stability in phosphate buffered saline and new-born calf serum. Micro-PET imaging at 1 h post injection of [(18)F]F-RGDfK showed medium concentration of radioactivity in tumors while much decreased concentration in tumors in the blocking group. These results showed that [(18)F]F-RGDfK obtained by click chemistry maintained the affinity and specificity of the RGDfK peptide to integrin α(v)β(3). This study provided useful information for peptide radiofluorination by using click chemistry.

Comparison of 16 mm OSU-Nag and COMS eye plaques

OSU‐NAG eye plaques use fewer sources than COMS‐plaques of comparable size, and do not employ a Silastic seed carrier insert. Monte Carlo modeling was used to calculate 3D dose distributions for a 16 mm OSU‐NAG eye plaque and a 16 mm COMS eye plaque loaded with either Iodine‐125 or Cesium‐131 brachytherapy sources. The OSU‐NAG eye plaque was loaded with eight sources forming two squares, whereas the COMS eye plaque was loaded with thirteen sources approximating three isocentric circles. A spherical eyeball 24.6 mm in diameter and an ellipsoid‐like tumor 6 mm in height and 12 mm in the major and minor axes were used to evaluate the doses delivered. To establish a fair comparison, a water seed carrier was used instead of the Silastic seed carrier designed for the traditional COMS eye plaque. Calculations were performed on the dose distributions along the eye plaque axis and the DVHs of the tumor, as well as the 3D distribution. Our results indicated that, to achieve a prescription dose of 85 Gy at 6 mm from the inner sclera edge for a six‐day treatment, the OSU‐NAG eye plaque will need 6.16 U/source and 6.82 U/source for  125I and  131Cs, respectively. The COMS eye plaque will require 4.02 U/source and 4.43 U/source for the same source types. The dose profiles of the two types of eye plaques on their central axes are within 9% difference for all applicable distances. The OSU‐NAG plaque delivers about 10% and 12% more dose than the COMS for  125I and  131Cs sources, respectively, at the inner sclera edge, but 6% and 3% less dose at the opposite retina. The DVHs of the tumor for two types of plaques were within 6% difference. In conclusion, the dosimetric quality of the OSU‐NAG eye plaque used in eye plaque brachytherapy is comparable to the COMS eye plaque. PACS number: 87.56B, 87.55k, 87.55kh

Design and development of compact readout electronics with silicon photomultiplier array for a compact imaging detector

This work aims at developing compact readout electronics for a compact imaging detector module with silicon photomultiplier (SPM) array. The detector module consists of a LYSO crystal array coupling with a SensLs 4x4 SPM array. A compact multiplexed readout based on a discretized positioning circuit (DPC) was developed to reduce the readout channels from 16 to 4 outputs. Different LYSO crystal arrays of 4x4, 8x8 and 12x12 with pixel sizes of 3.2, 1.6 and 1.0 mm respectively, have been tested with the compact readout board using a Cs-137 source. The initial results show that the compact imaging detector module with the compact multiplexed readout could clearly resolve 1 mmx1 mmx10 mm LYSO scintillation crystal array except those at the edges. The detectors intrinsic spatial resolution up to 1 mm can be achieved with the 3 mmx3 mm size SPMArray4 through light sharing and compact multiplexed readout. Our results indicate that this detector module is feasible for the development of high-resolution compact PET.

Characterization of prompt gamma-ray emission with respect to the Bragg peak for proton beam range verification: A Monte Carlo study

In this paper we report a Geant4 simulation study to investigate the characteristic prompt gamma (PG) emission in a water phantom for real-time monitoring of the Bragg peak (BP) during proton beam irradiation. The PG production, emission spatial correlation with the BP, and position preference for detection with respect to the BP have been quantified in different PG energy windows as a function of proton pencil-beam energy from 100 to 200MeV. The PG response to small BP shifts was evaluated using a 2cm-thick slab with different human body materials embedded in a water phantom. Our results show that the prominent characteristic PG emissions of 4.44, 5.21 and 6.13MeV exhibit distinctive correlation with the dose deposition curve. The accuracy in BP position identification using these characteristic PG rays is highly consistent as the beam energy increases from 100 to 200MeV. There exists a position preference for PG detection with respect to the BP position, which has a strong dependence on the proton beam energy and PG energies. It was also observed that a submillimeter shift of the BP position can be realized by using PG signals. These results indicate that the characteristic PG signal is sensitive and reliable for BP tracking. Although the maximization of the PG measurement associated with the BP is difficult, it can be optimized with energy and detection position preferences.

Study on retinal dopamine transporter in form deprivation myopia using the radiopharmaceutical tracer 99mTc-TRODAT-1.

PurposeTo investigate the distributions and changes in dopamine transporters (DATs) using 99mTc-TRODAT-1 ([99mTc-(2((2-(((3-(4-chlorophenyl)-8-methyl-8-azabicyclo(3,2,1)-oct-2-yl)-methyl)(2-mercaptoethyl)amino)ethyl)amino)ethane-thiolato(3-)-N2,N2′,S2,S2)oxo-(1R-(exo-exo)))]) in form deprivation myopia retina. MethodsPigmented guinea pigs aged 3 weeks were randomly assigned into two groups: form-deprivation myopia and normal control group. The test group wore a translucent goggle covering randomly for 4 weeks, and both groups underwent biometric measurement before and after the experiment. Both Micro-single-photon emission computed tomography (SPECT) imaging and ex-vivo autoradiography were performed with the injection of 99mTc-TRODAT-1 on the 4th week for all the guinea pigs. ResultsThe retinas were clearly resolved with 99mTc-TRODAT-1 in both Micro-SPECT imaging and ex-vivo autoradiography. In Micro-SPECT imaging, the ratio of 99mTc-TRODAT-1 uptake in the myopic retinas (11.55±2.80) was 3.64±1.40 lower than that in the normal control eyes (15.20±1.98, P=0.026, F=2.94, t=2.605), and 2.35±1.05 lower than that in the fellow eyes (13.90±2.04, P=0.003, t=5.476). In ex-vivo autoradiography, the ratio of 99mTc-TRODAT-1 uptake in the myopic retina (95.52±12.04) was 18.54±5.86 lower than in the normal control eyes (114.06±7.81, P=0.01, F=0.331, t=3.164), and was 16.95±5.78 lower than in the fellow eyes (112.47±15.67, P=0.001, t=7.179). Conclusion99mTc-TRODAT-1 can be used to trace the distributions and changes in DAT in the retina. DATs in the myopic retinas were lower than that in the fellow and normal control eyes. Radionuclide tracing may provide a new approach in vivo for further studies on the dopamine system in myopia.

High-resolution SPECT for small-animal imaging

Abstract This article presents a brief overview of the development of high-resolution SPECT for small-animal imaging. A pinhole collimator has been used for high-resolution animal SPECT to provide better spatial resolution and detection efficiency in comparison with a parallel-hole collimator. The theory of imaging characteristics of the pin-hole collimator is presented and the designs of the pinhole aperture are discussed. The detector technologies used for the development of small-animal SPECT and the recent advances are presented. The evolving trend of small-animal SPECT is toward a multi-pinhole and a multi-detector system to obtain a high resolution and also a high detection efficiency.