Pharmacoimaging of Blood-Brain Barrier Permeable (FDG) and Impermeable (FLT) Substrates After Intranasal (IN) Administration.

To illustrate the use of imaging to quantify the transfer of materials from the nasal cavity to other anatomical compartments, specifically, transfer to the brain using the thymidine analogue, [18F]fluorothymidine (FLT), and the glucose analogue, [18F]fluorodeoxyglucose (FDG). Anesthetized rats were administered FLT or FDG by intranasal instillation (IN) or tail-vein injection (IV). PET/CT imaging was performed for up to 60 min. Volumes-of-interest (VOIs) for the olfactory bulb (OB) and the remaining brain were created on the CT and transferred to the co-registered dynamic PET. Time-activity curves (TACs) were generated and compared. The disposition patterns were successfully visualized and quantified and differences in brain distribution patterns were observed. For FDG, the concentration was substantially higher in the OB than the brain only after IN administration. For FLT, the concentration was higher in the OB than the brain after both IN and IV and higher after IN than after IV administration at all times, whereas the concentration in the brain was higher after IN than after IV administration at early times only. Approximately 50 and 9% of the IN FDG and FLT doses, respectively, remained in the nasal cavity at 20 min post-administration. The initial phase of clearance was similar for both agents (t1/2 = 2.53 and 3.36 min) but the slow clearance phase was more rapid for FLT than FDG (t1/2 = 32.1 and 85.2 min, respectively). Pharmacoimaging techniques employing PET/CT can be successfully implemented to quantitatively investigate and compare the disposition of radiolabeled agents administered by a variety of routes.

A new automated NaCl based robust method for routine production of gallium-68 labeled peptides.

A new NaCl based method for preparation of gallium-68 labeled radiopharmaceuticals has been adapted for use with an automated gallium-68 generator system. The method was evaluated based on 56 preparations of [(68)Ga]DOTATOC and compared to a similar acetone-based approach. Advantages of the new NaCl approach include reduced preparation time (<15 min) and removal of organic solvents. The method produces high peptide-bound % (>97%), and specific activity (>40 MBq nmole(-1) [(68)Ga]DOTATOC) and is well-suited for clinical production of radiopharmaceuticals.

Technical issues in the determination of cerebrovascular reserve in elderly subjects using 15O-water PET imaging.

The accurate determination of cerebrovascular reserve (CVR), especially in elderly subjects, entails several technical issues. From a review of the literature, the optimal technique employs quantitative 15O-water PET imaging determinations of cerebral blood flow (CBF) and acetazolamide (ACZ) (1 g iv with measurements at 10- to 20-min post-administration) as the vasodilating agent. CBF and CVR measurements were made using this methodology on 12 elderly subjects (3 males, 9 females, 66-84 years of age) meeting criteria for mild cognitive impairment (MCI) without other significant medical problems. Applying this quantitative technique, the cognitive and emotional status of the subject during the imaging procedure influenced the magnitude of the measurements. The semiquantitative measures resulted in even more pronounced subject state influences. The conditions under which CBF or CVR measurements are made should be controlled and reported. If semiquantitative techniques (e.g., single-photon emission-computed tomography [SPECT] imaging) must be employed for the determination of CVR, the validity of any measurement is dependent on the careful control of the general physiological status (e.g., heart rate, blood pressure, level of anxiety) of the patient.