Xuezhu Zhang

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.

Unified geometric calibration and image registration for detached small animal SPECT/CT

The aim of this study is to develop a unified optimization method to estimate the complete parameters about geometric calibration of system misalignment for both cone-beam CT and pinhole SPECT, and parameters about coordinate transformation of image registration for these detached systems. The uniform projection equations are derived for both cone-beam and pinhole imaging geometry. Complete geometric parameters are estimated by point object phantom with a priori relative position information. The cost function is structured as the least-squares about residual error. The implementation of nonlinear estimation utilizes the Powell method so as to constrain the optimization problem of this study to converge to the unique solution. The registration procedure is also implemented by the nonlinear optimization method similar to the geometric calibration, and six parameters are sufficient to register the detached systems for multi-modality image fusion. We designed a general-purpose point object/sources phantom for both geometric calibration and image registration procedures. To validate the method presented, we performed small animal experiment studies based on our Micro-SPECT and Micro-CT systems. The results from the imaging experiments show that the unified estimation method is considerable effective and robust for detached multi-modality Micro-SPECT/CT systems.

Implementing analytical geometric and penetration response correction for keel-edge pinhole SPECT image reconstruction

The collimator response compensation is very important in high-resolution pinhole SPECT imaging for resolution recovery and quantitative imaging. In this study the pinhole collimator response of the keel-edge aperture was investigated in terms of the geometric response function and penetration response function (GPRF). An approximate numerical method was proposed to implement the geometric and penetration response correction (GPRC) for keel-edge pinhole SPECT image reconstruction. A lookup table for the GPRC was calculated and then was utilized in the 3D pinhole iterative OSEM reconstruction procedure. The performance of the image reconstruction with the GPRC was evaluated using both the phantom and small-animal experiments in our micro-SPECT system. The results demonstrated significant improvements in the reconstructed image quality and resolution recovery. In conclusion, our approach using the GPRC method to the resolution recovery for the pinhole SPECT imaging is effective.

Development of a simplified readout for a compact gamma camera based on 2×2 H8500 multi-anode PSPMT array

The aim of this study was to develop a highperformance simplified readout electronic for a compact gamma camera to achieve a maximized performance in its intrinsic spatial resolution. This compact camera is based on a pixellated NaI(Tl) crystal with 1.2mm×1.2mm×5 mm pixel element and 1.4 mm pixel pitch coupled to a 2×2 Hamamatsu H8500 multi-anode position sensitive photomultiplier tube (PSPMT) array. The design of the simplified readout is based on novel two-stage charge divisions with Truncated Center-of-Gravity (TCOG) positioning method to maximize the detector performance. The performance of the compact camera with the novel simplified readout was evaluated by flood imaging of a 57Co source. The experimental results show that the readout circuits we developed can effectively reduce the readout channels from 256 to 4 and well resolve the 1.2mm crystal elements of the NaI(Tl) crystal array while maximizing the effective field-of-view (FOV) of the detector to cover the whole active area of the detector. In addition, the optical coupling measures in the gap regions among the PSPMT array are necessary in order to improve the image distortion in the gap regions. The results indicate that our design is effective approach which can be adopted for other highresolution gamma camera based on multi-anode PSPMT array with a larger FOV.

Feasibility of 99mTc-TRODAT-1 Micro-SPECT imaging of dopamine transporter in animal retinas

In this paper, (99m)Tc-TRODAT-1 Micro-SPECT (single-photon emission computed tomography) was used for imaging dopamine transporter (DAT) in retinas and to investigate the changes of DAT in retinas of pigs with form deprivation myopia. Pigmented guinea pigs aged 3 weeks were devided into form deprivation myopia (FDM) group (n=6) and normal control group (n=6). The test group wore translucent goggles randomly for 4 weeks, and both groups underwent biometric measurement (refraction and axial length) before and after the experiment. Micro-SPECT retinas imaging was performed at the 4(th) week after injection of (99m)Tc-TRODAT-1. The retinas were clearly resolved in the images. The ratio of (99m)Tc-TRODAT-1 uptake in the myopic retinas (11.55 +/- 2.80) was 3.64 +/- 1.40 lower than that in the control eye (15.20 +/- 1.98), and 2.35 +/- 1.05 lower than that in the fellow eyes (13.90 +/- 2.04). The results showed that (99m)Tc-TRODAT-1 Micro-SPECT eye imaging can be used to trace the distribution and changes of DAT in retina, and DAT in the myopic retinas were lower than that in the normal control eyes and fellow eyes. Micro-SPECT may provide a new approach for further studies on the role of dopamine system in the experimental myopia.