Blood brain barrier permeability assessment

The Rb-82 generator permits serial studies in the same patient as often as every 10 minutes with 20-60 mCi of Rb-82 for rapid bolus intravenous infusion. Inherent in the administration of high levels of Rb-82 activity is the need for precise flow control from an automated system to deliver the desired amount of radioactivity. The development of the alumina column parameters and the elution protocol as well as the automated microprocessor system controller are presented here. Some of the details of this system have been discussed in earlier publications (15,21). Generator produced Rb-82 is used as a diffusible flow tracer in myocardial perfusion studies and as a nondiffusible tracer in brain studies to assess blood brain barrier permeability changes in patients with brain tumors or Alzheimer s type dementia. 

Pozzilli C, Bemai di S, Mansi L, Picozzi P, lannotti F, Alfano B, Bozzao L, Lenzi GL, Salvatore M, Conforti P, Fieschi C (1988) Quantitative assessment of the blood-brain barrier permeability in multiple sclerosis using 68-Ga-EDTA and positron emission tomogi aphy. J Neurol Neurosurg Psych 51 1058—1062. 

Hallier-Vanuxeem D, Prieto P, Culot M, et al. New strategy for alerting central nervous system toxicity integration of blood-brain barrier toxicity and permeability in neurotoxicity assessment. Toxicol In Vitro. 2009 23 447-453. 

Chu I, Liu F, Soares A, Kumari P, Nomeir AA. Generic fast gradient liquid chromatography/ tandem mass spectrometry techniques for the assessment of the in vitro permeability across the blood-brain barrier in drug discovery Rapid Common Mass Spectrom 2002 16(15) 1501-1505. 

A Summary of Clinical Pharmacology Studies is to provide reviewers of a marketing application with an overall view of the clinical pharmacology of a drug candidate and is to include information on clinical studies conducted to evaluate human PK and PD and on in vitro studies performed with human cells, tissues, or related material (i.e., human biomaterials) and considered pertinent to PK processes. Types of in vitro studies include permeability assessment (e.g., intestinal absorption, blood-brain barrier transport, protein... 

Any assessment of the central effects of noradrenaline following its parenteral administration has to be made with care since the blood-brain barrier has a limited permeability to the catecholamines. The feelings of anxiety and apprehension reported by subjects who have received adrenaline... 

---