The Radiopharmaceutical Chemistry Laboratory
The radiopharmaceutical chemistry research program of Nuclear Medicine and Molecular Imaging at Boston Children's Hospital, directed by Alan B. Packard, Ph.D., is currently engaged in four active radiopharmaceutical chemistry research programs. These programs include:
Development of New PET Radiopharmaceuticals for Measuring Multidrug Resistance
The objective of this project is the development of 64Cu radiopharmaceuticals that are substrates for Pgp, the protein implicated in multidrug resistance (MDR) so that these compounds can be used to measure MDR prior to the initiation of chemotherapy. This project is supported by an NCI R01 Award to Dr. Packard.
Evaluation of Novel 64Cu Chelates of Engineered CH2-deleted Anti-GD2 IgG for PET Imaging
The objective of this project is the evaluation of a new 64Cu chelator for labeling monoclonal antibodies. In contrast to existing chelators, this new chelator, a derivative of a ligand known as diamsar, does not allow 64Cu to be released in vivo, eliminating the problem of high 64Cu uptake in non-target tissue, such as the liver. This is a collaborative project between Dr. Suzanne Smith (ANSTO), Dr. Jim Huston (EMD-Serono), and Dr. Packard. The project is currently supported by an NCI K08 award on which Dr. Packard is a mentor.
MicroSPECT Measurement of Response to Treatment with anti-αvβ3 Chemotherapeutics using a 99mTc-labeled RGD Peptide
The objective of this project is to determine if it is possible to use in vivo imaging with microSPECT and NC100692, a 99mTc-labeled RGD-containing peptide, to measure treatment response to an anti-αvβ3compound using an intracranial U87 model in the mouse. This project is a collaboration between Dr. Mark Kieran (Dana-Farber Cancer Institute), GE Healthcare, the HMS microSPECT facility, and Dr. Packard. This project is supported by a grant from the Boston Children's Brain Tumor Foundation on which Dr. Packard is a co-investigator.
Synthesis and In Vivo Characterization of a Novel 18F-labeled Lipophilic Cation for the PET Measurement of Myocardial Perfusion.
This is a pilot project to prepare an 18F-labeled analog of a cationic compound that is already known to accumulate in mitochondria. The unlabeled version of the target compound shows several biological similarities to 99mTc-MIBI suggesting that is should be an effective marker of myocardial perfusion and may also be a substrate for Pgp, and thus an 18F-labeled marker of multidrug resistance.
The radiopharmaceutical chemistry research program occupies two research laboratories in the Enders research building at Children's: a radiopharmaceutical chemistry laboratory and a "hot" laboratory. A separate cell-culture laboratory is also available.
The radiopharmaceutical chemistry laboratory contains four fume hoods, approximately 50 linear feet of bench space, and is set up to accommodate three postdoctoral researchers. The laboratory is equipped with various chemical instrumentation including a Bruker FTIR spectrometer, a Perkin-Elmer Lambda 40 uv-visible spectrophotometer, and a Hitachi high-performance liquid chromatograph equipped with a diode array and a gamma detector. Other smaller pieces of equipment (centrifuges, pH meters, etc.) are also available.
The hot laboratory is used for handling high levels of radioactivity and has a shielded fume hood that is equipped with a pair of Tru-Motion remote manipulator arms. This laboratory is also equipped with a semi-preparative HPLC system for purification of 18F-labeled compounds. This laboratory is scheduled for renovation in the spring of 2008. The renovation will include the addition of a hot cell suitable for the preparation of higher levels of 18F-labeled compounds than can be accommodated in the existing facility. In addition to our own basic science investigations, this laboratory is also used for the preparation of 18F-labeled compounds for use by CHB microPET users.
Small Imaging Laboratory (SAIL)
In recognition of the value of small animal imaging to the research community, Boston Children's Hospital has committed to developing a state-of-the-art Small Animal Imaging Laboratory. The SAIL facility is located within the Department of Radiology's Kresge Laboratory. The instrumentation available to researchers includes:
Siemens Focus 120 microPET
The Siemens Focus 120 MicroPET is a high-resolution, small animal PET scanner that combines high spatial resolution (<1.3 mm) and high sensitivity (>7%) with a bore size (12 cm diameter and 7.6 axial length) that is optimized for imaging mice and rats. Among commercially available radioactive agents, we are routinely imaging with 18F 2-fluoro-2-deoxy-D-glucose (FDG) and 18F sodium fluoride. We have also carried out some microPET studies with 18F fluorothymidine (FLT) provided by the Division of Nuclear Medicine at Massachusetts General Hospital; we have validated the synthesis of 18F FHBG and have carried out preliminary studies with this tracer; and we are developing a new 18F-labeled ?v?3 imaging agent.
Siemens microCAT II
The Siemens microCAT II is a high-resolution (27 microns in standard mode and 15 microns in high-resolution mode) CT scanner designed specifically for imaging small animals such as mice and rats. The radiation detector is configurable such that, for mice, the transaxial field of view is 5.4 cm and the axial field of view is 8 cm; whereas, for rats, the transaxial field of view is 8 cm and the axial field of view is 5.4 cm. We have utilized microCT for tumor imaging, for anatomical correlation for microPET studies, and for ex vivo imaging (e.g., structural analysis of porcine cardiac valves).
VisualSonics Vevo 2100 Ultrasound
The laboratory is equipped with a VisualSonics Vevo 2100 small animal ultrasound system. This is a high-resolution instrument (30 microns) that can also image at high speed (up to 100 frames per second). It is capable of imaging in 3D mode as well as M mode, and can also provide pulsed wave Doppler imaging. The device is equipped with two transducers (25 and 40 MHz) and the Vevo Integrated Rail System, which facilitates alignment of the mouse and the probe as well as image-guided injection, when necessary. The table is heated and includes sensor pads for monitoring the animal during examination. The system is routinely used for cardiac imaging in small animals.
ADC/XRE Unicath SP Fluoroscopy
Large-animal fluoroscopy is available using an ADC/XRE Unicath SP single-plane cardiovascular digital angiography unit with a high-resolution fluoroscopy tube, an advanced image intensifier with full-frame zoom, and an image analysis workstation.
Faxitron MX-20 Specimen Radiograph System X-ray
The Faxitron MX-20 Specimen Radiograph System provides high-resolution x-ray images of mice and small rats (the system includes a gas anesthesia system) as well the ability to obtain radiographic images of excised tissue samples. The x-ray tube can operate at voltages ranging from 10 to 35 kVp with a maximum tube current of 300 ?A. The focal spot is 20 ?m allowing for very high spatial resolution. The system is mounted on a cart and can be moved around the laboratory as necessary.