First image from a combined positron emission tomography and field-cycled MRI system.

Combining positron emission tomography and MRI modalities typically requires using either conventional MRI with a MR-compatible positron emission tomography system or a modified MR system with conventional positron emission tomography. A feature of field-cycled MRI is that all magnetic fields can be turned off rapidly, enabling the use of conventional positron emission tomography detectors based on photomultiplier tubes. In this demonstration, two photomultiplier tube-based positron emission tomography detectors were integrated with a field-cycled MRI system (0.3 T/4 MHz) by placing them into a 9-cm axial gap. A positron emission tomography-MRI phantom consisting of a triangular arrangement of positron-emitting point sources embedded in an onion was imaged in a repeating interleaved sequence of ∼1 sec MRI then 1 sec positron emission tomography. The first multimodality images from the combined positron emission tomography and field-cycled MRI system show no additional artifacts due to interaction between the systems and demonstrate the potential of this approach to combining positron emission tomography and MRI.

An Aspartyl Cathepsin Targeted PET Agent: Application in an Alzheimer's Disease Mouse Model.

BACKGROUND: Early detection of Alzheimer's disease (AD) pathology is a serious challenge for both diagnosis and clinical trials. The aspartyl protease, Cathepsin D (CatD), is overexpressed in AD and could be a biomarker of disease. We have previously designed a unique contrast agent (CA) for dual-optical and magnetic resonance imaging of the activity of the CatD class of enzymes. OBJECTIVE: To compare the uptake and retention of a novel, more sensitive, and clinically-translatable 68Ga PET tracer targeting CatD activity in 5XFAD mice and non-Tg littermates. METHODS: The targeted CA consisted of an HIV-1 Tat cell penetrating peptide (CPP) conjugated to a specialized cleavage sequence targeting aspartyl cathepsins and a DOTA conjugate chelating 68Ga. PET images were acquired using a Siemens Inveon preclinical microPET in female Tg AD mice and non-Tg age matched female littermates (n = 5-8) following intravenous CA administration at 2, 6, and 9 months of age. Additionally, 18F fluorodeoxyglucose (FDG) PET imaging was performed at 10 months to measure glucose uptake. RESULTS: The Tg mice showed significantly higher relative uptake rate of the targeting CA in the forebrain relative to hindbrain at all ages compared to controls, consistent with histology. In contrast, no differences were seen in CA uptake in other organs. Additionally, the Tg mice did not show any differences in relative uptake of FDG at 10 months of age in the forebrain relative to the hindbrain compared to age matched non-Tg controls. CONCLUSIONS: Elevated aspartryl cathepsin activity was detected in vivo in the 5XFAD mouse model of AD using a novel targeted PET contrast agent.