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James M Woolfenden

Publications and source records attributed to James M Woolfenden.

5 recordsLinked to original sources

SemiSPECT: a small-animal single-photon emission computed tomography (SPECT) imager based on eight cadmium zinc telluride (CZT) detector arrays.

The first full single-photon emission computed tomography (SPECT) imager to exploit eight compact high-intrinsic-resolution cadmium zinc telluride (CZT) detectors, called SemiSPECT, has been completed. Each detector consists of a CZT crystal and a customized application-specific integrated circuit (ASIC). The CZT crystal is a 2.7 cm x 2.7 cm x -0.2 cm slab with a continuous top electrode and a bottom electrode patterned into a 64 x 64 pixel array by photolithography. The ASIC is attached to the bottom of the CZT crystal by indium-bump bonding. A bias voltage of -180 V is applied to the continuous electrode. The eight detectors are arranged in an octagonal lead-shielded ring. Each pinhole in the eight-pinhole aperture placed at the center of the ring is matched to each individual detector array. An object is imaged onto each detector through a pinhole, and each detector is operated independently with list-mode acquisition. The imaging subject can be rotated about a vertical axis to obtain additional angular projections. The performance of SemiSPECT was characterized using 99mTc. When a 0.5 mm diameter pinhole is used, the spatial resolution on each axis is about 1.4 mm as estimated by the Fourier crosstalk matrix, which provides an algorithm-independent average resolution over the field of view. The energy resolution achieved by summing neighboring pixel signals in a 3 x 3 window is about 10% full-width-at-half-maximum of the photopeak. The overall system sensitivity is about 0.5 x 10(-4) with the energy window of +/-10% from the photopeak. Line-phantom images are presented to visualize the spatial resolution provided by SemiSPECT, and images of bone, myocardium, and human tumor xenografts in mice demonstrate the feasibility of preclinical small-animal studies with SemiSPECT.

Animals↗

Imaging recognition of inhibition of multidrug resistance in human breast cancer xenografts using 99mTc-labeled sestamibi and tetrofosmin.

BACKGROUND: (99m)Tc-sestamibi (MIBI) and (99m)Tc-tetrofosmin (TF) are avid transport substrates recognized by the multidrug resistance (MDR) P-glycoprotein (Pgp). This study was designed to compare the properties of MIBI and TF in assessing the inhibition of Pgp by PSC833 in severe combined immunodeficient mice bearing MCF7 human breast tumors using SPECT imaging. METHODS: Animals with drug-sensitive (MCF/WT) and drug-resistant (MCF7/AdrR) tumors were treated by PSC833 and by carrier vehicle 1 h before imaging, respectively. Dynamic images were acquired for 30 min after intravenous injection of MIBI/TF using a SPECT system, FastSPECT. The biodistribution of MIBI and TF was determined at the end of the imaging session. RESULTS: MCF7/WT in the absence and presence of PSC833 could be visualized by MIBI and TF imaging within 5 min and remained detectable for 30 min postinjection. MCF7/AdrR could be visualized only 2-5 min without PSC833 treatment but could be detected for 30 min with PSC833, very similar to MCF7/WT. MCF7/AdrR without PSC833 showed significantly greater radioactive washout than MCF7/WT and MCF7/AdrR with PSC833 treatment. PSC833 increased the accumulation (%ID/g) in MCF7/AdrR 3.0-fold (1.62+/-0.15 vs. 0.55+/-0.05, P<.05) for TF and 1.9-fold (1.21+/-0.04 vs. 0.64+/-0.05, P<.05) for MIBI but did not affect MCF7/WT. CONCLUSIONS: The feasibility of MIBI and TF for assessment of MDR expression and inhibition was demonstrated in mice through FastSPECT imaging. The results indicate that TF may be at least comparable with MIBI in recognizing Pgp expression and modulation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Imaging recognition of multidrug resistance in human breast tumors using 99mTc-labeled monocationic agents and a high-resolution stationary SPECT system.

Imaging recognition of multidrug-resistance by 99mTc-labeled sestamibi, tetrofosmin and furifosmin in mice bearing human breast tumors was evaluated using a high-resolution SPECT, FASTSPECT. Imaging results showed that the washout rates in drug-resistant MCF7/D40 tumors were significantly greater than that in drug-sensitive MCF7/S tumors. Furifosmin exhibited greater washout from both MCF7/S and MCF7/D40 than sestamibi, while tetrofosmin washout was greater than sestamibi in MCF7/D40 only. Feasibility of the monocationic agents for characterizing MDR expression was well clarified with FASTSPECT imaging.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

99mTc glucarate high-resolution imaging of drug sensitive and drug resistant human breast cancer xenografts in SCID mice.

BACKGROUND AND AIM: Previous studies have showed that 99mTc labelled glucarate (GLA) might be an agent for non-invasive detection of breast tumours. In xenografted BT20 breast tumours, GLA was found to have higher uptake than 99mTc sestamibi (MIBI). It is unclear whether GLA can localize in all cell line breast cancer xenografts, as well as breast tumours with multidrug resistance (MDR). The present study aimed to investigate the properties of GLA in detecting drug sensitive and drug resistant MCF7 breast cancer xenografts in mice by using dynamic single photon emission computed tomography (SPECT) imaging. METHODS: MCF7/S cells are drug sensitive breast carcinoma cells. MCF7/D40 cells are 40-fold more resistant to doxorubicin compared to MCF7/S. Subcutaneous tumours were grown in SCID mice for 10-14 days after injection of 1 x 10(6) cells into the right thigh. Anaesthetized mice with MCF7/S (MIBI, n=9; GLA, n=8) and MCF7/D40 (MIBI, n=6; GLA, n=5) tumours were imaged using a high-resolution SPECT system called FASTSPECT. Dynamic images were acquired for 2 h after intravenous injection of GLA or MIBI. Expression of MDR P-glycoprotein (Pgp) in the tumours was demonstrated in the MCF7/D40 tumours by western blotting, not in the MCF7/S tumours. RESULTS: The xenografted tumours were visualized unequivocally within 10-30 min in GLA images and remained detectable for at least 2 h after injection. Drug resistant tumours, from which MIBI was rapidly expelled, retained GLA as readily as did drug sensitive tumours. The biodistribution data of GLA demonstrated significantly higher accumulation (%ID/g) compared to MIBI. CONCLUSION: MCF7 tumour xenografts can be detected by 99mTc glucarate imaging. More importantly, 99mTc glucarate can potentially localize drug resistant breast tumours.

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