Noninvasive imaging at the molecular level is an emerging field in biomedical research. This paper introduces a new technology synergizing two leading imaging methodologies: positron emission tomography (PET) and magnetic resonance imaging (MRI). Although the value of PET lies in its high-sensitivity tracking of biomarkers in vivo, it lacks resolving morphology. MRI has lower sensitivity, but produces high soft-tissue contrast and provides spectroscopic information and functional MRI (fMRI). We have developed a three-dimensional animal PET scanner that is built into a 7-T MRI. Our evaluations show that both modalities preserve their functionality, even when operated isochronously. With this combined imaging system, we simultaneously acquired functional and morphological PET-MRI data from living mice. PET-MRI provides a powerful tool for studying biology and pathology in preclinical research and has great potential for clinical applications. Combining fMRI and spectroscopy with PET paves the way for a new perspective in molecular imaging.

emission intensities were measured at 450 and 480 mm with readings being taken directly off the microphotometer. Tubes were then opened and aerated; the residual signal was measured and subtracted from that of the unopened tube. Emission spectra recorded on a Houston X-Y recorder were identical with those reported for benzophenone in other solvent^.^' EPR spectra of the biphenyls were obtained in both ethanol and methylcyclohexane glasses at 77 O K on a Varian E-4 EPR spectrometer. The light from a 1 kW high-pressure mercury-xenon arc, filtered only through water, was focused directly onto the cavity.Phosphorescence spectra of the biphenyls were obtained at 77 O K on the Aminco with the phosphoroscope attachment. Excitation was at 254 mm. Biphenyl concentrations were approximately IO-2 M. Absorption spectra were obtained on a Cary 14.Abstract: Hot homolytic aromatic chlorination has been studied in simple monosubstituted benzenes CsHsX (X = F, C1, Br, 1, NH2, OCH3, NOn) using recoil chlorine atoms produced via the 37Cl(n,y)38CI reaction. In the gas phase, CI-for-H substitution is a minor process, proceeding exclusively via hot direct replacement with little selectivity. In the liquid phase, dilution experiments reveal that two processes contribute to hydrogen substitution: a one-step reaction being first order with respect to the concentration of the aromatic substrate and a multistep process involving at least two substrate molecules. In either case the CI atoms exhibit slight electrophilic features. Application of the Hammett correlation reveals a higher selectivity (pf = -1.43) for the multistep than for the one step process (p+ = -0.56). Both chlorination reactions seem to proceed via complex formation. In the case of CI-for-X substitution, thermoneutral or exothermic processes (X = CI, Br, I, NOl) can be attributed to thermal a-complex formation, while endothermic processes (X = F, OCH3, NH2) are typically low yield, direct hot replacement reactions being first order with respect to the substrate concentration.

The aim of this study was to evaluate the use of [(18)F]fluorothymidine (FLT) as a positron emission tomography (PET) tracer for the diagnosis of breast cancer. To this end, 12 patients with 14 primary breast cancer lesions (T2-T4) were studied by FLT-PET. For comparison, [(18)F]fluorodeoxyglucose (FDG) PET scans were performed in six patients. Thirteen of the 14 primary tumours demonstrated focally increased FLT uptake (SUV(mean)=3.4+/-1.1). Seven out of eight patients with histologically proven axillary lymph node metastases showed focally increased FLT uptake in the corresponding areas (SUV(mean)=2.4+/-1.2). The lowest SUV (mean =0.7) was observed in one of two inflammatory cancers. The contrast between primary tumours or metastases and surrounding tissue was high in most cases. In direct comparison to FDG-PET, the SUVs of primary tumours (5/6) and axillary lymph node metastases (3/4) were lower in FLT-PET (SUV(FLT): 3.2 vs SUV(FDG): 4.7 in primary tumours and SUV(FLT): 2.9 vs SUV(FDG): 4.6 in lymph node metastases). Since FLT uptake in surrounding breast tissue was also lower, tumour contrast was comparable to that with FDG. It is of note that normal FLT uptake was very low in the mediastinum, resulting in a higher tumour-to-mediastinum ratio as compared to FDG ( P=0.03). FLT-PET is suitable for the diagnosis of primary breast cancer and locoregional metastases. High image contrast may facilitate the detection of small foci, especially in the mediastinum.

Background:The spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of autosomal dominant ataxias: some mutations, including SCA1, SCA2, and SCA3, are multisystemic disorders characterized by a variety of noncerebellar symptoms while others, like SCA6, give rise to a pure cerebellar syndrome.Objective: To identify impairments of the dopaminergic system and regional changes of glucose metabolism in SCA1, SCA2, SCA3, and SCA6. Methods:We used [ 11 C]d-threo-methylphenidate and [ 18 F]fluorodeoxyglucose positron emission tomography to identify cerebral dopamine terminal loss and specific regional metabolic patterns in SCA1, SCA2, SCA3, and SCA6. Results:The binding potential of [ 11 C]d-threo-methylphenidate was reduced in the striatum in SCA2 and SCA3; in contrast to patients with Parkinson disease, no increased susceptibility of the putamen was evident. Decreased regional cerebral glucose metabolism was found in the cerebellum of all patients with SCA, the brainstem of SCA1, SCA2, SCA3, the thalamus and putamen of SCA3, and the parietal cortex of patients with SCA2. A trend toward increased regional cerebral glucose metabolism was found in the temporal cortex of all patients with SCA, pronounced in SCA6.Conclusions: Specific biochemical patterns point to different mechanisms of neuronal dysfunction in SCA1, SCA2, SCA3, and SCA6; dopamine terminal loss is severe in SCA2 but distinct from Parkinson disease.

Prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein, is highly expressed by virtually all prostate cancers and is currently the focus of several diagnostic and therapeutic strategies. We have previously reported on the generation of several monoclonal antibodies (mAb) and antibody fragments that recognize and bind with high affinity to the extracellular domain of cell-adherent PSMA. This article reports the in vivo behavior and tumor uptake of the radiolabeled anti-PSMA mAb 3/A12 and its potential as a tracer for PET. Methods: The mAb 3/A12 was conjugated with the chelating agent 1,4,7,10-tetraazacyclododecane-N,N9,N$,N9$-tetraacetic acid (DOTA) and radiolabeled with 64 Cu. Severe combined immunodeficient mice bearing PSMA-positive C4-2 prostate carcinoma xenografts were used for small-animal PET imaging. Mice with PSMA-negative DU 145 tumors served as controls. For PET studies, each animal received 20-30 mg of radiolabeled mAb corresponding to an activity of 7.6-11.5 MBq. Imaging was performed 3, 24, and 48 h after injection. After the last scan, the mice were sacrificed and tracer in vivo biodistribution was measured by g-counting. Results: Binding of the mAb 3/A12 on PSMA-expressing C4-2 cells was only minimally influenced by DOTA conjugation. The labeling efficiency using 64 Cu and DOTA-3/A12 was 95.3% 6 0.3%. The specific activity after 64 Cu labeling was between 327 and 567 MBq/mg. After tracer injection, static small-animal PET images of mice with PSMA-positive tumors revealed a tumor-to-background ratio of 3.3 6 1.3 at 3 h, 7.8 6 1.4 at 24 h, and 9.6 6 2.7 at 48 h. In contrast, no significant tracer uptake occurred in the PSMA-negative DU 145 tumors. These results were confirmed by direct counting of tissues after the final imaging. Conclusion: Because of the high and specific uptake of 64 Cu-labeled mAb 3/A12 in PSMA-positive tumors, this ligand represents an excellent candidate for prostate cancer imaging and potentially for radioimmunotherapy.