title: In vitro binding of [³H]PIB to human amyloid deposits of different types.
abstract: Systemic amyloidosis is caused by extracellular deposition of insoluble fibrillar proteins arranged in β-pleated sheets. [(11)C]PIB has been used in PET studies to assess Aβ deposition in brain of patients with Alzheimer's disease (AD). The possibility to visualize other types of amyloid deposits with [(11)C]PIB would be of potential clinical importance in early diagnosis and for following therapeutic effects. In the present study, we evaluated in vitro binding of [(3)H]PIB to tissues containing transthyretin (ATTR), immunoglobulin light-chain (AL), amyloid protein A (AA) and Aβ amyloid. We found significantly higher binding of [(3)H]PIB in tissue from systemic amyloidoses than in control tissue, i.e. 4.7 times higher (p < 0.05). [(3)H]PIB showed the highest affinity to cortex of AD brain (IC50 = 3.84 nM), while IC50 values were much higher for ATTR, AA and AL type of amyloidosis and large variations in affinity were observed even within tissues having the same type of amyloidosis. Extraction with guanidine-HCl, which disrupts the β-sheet structure, decreased the protein levels and, concomitantly, the binding of [(3)H]PIB in all four types of amyloidoses.
authors.affiliation: Department of Medicinal Chemistry, Preclinical PET Platform .
authors.forename: Ewa
authors.initials: E
authors.lastname: Hellström-Lindahl
authors.forename: Per
authors.initials: P
authors.lastname: Westermark
authors.forename: Gunnar
authors.initials: G
authors.lastname: Antoni
authors.forename: Sergio
authors.initials: S
authors.lastname: Estrada
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry; D000814:Aniline Compounds / Q000737:chemistry*; D016022:Case-Control Studies; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000737:chemistry; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000737:chemistry*; D011228:Prealbumin / Q000737:chemistry; D011485:Protein Binding; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000737:chemistry*; D000685:Serum Amyloid A Protein / Q000737:chemistry; D013844:Thiazoles / Q000737:chemistry*; D014020:Tissue Extracts / Q000737:chemistry; D014316:Tritium / Q000737:chemistry*
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016564:Amyloid beta-Protein Precursor; D000814:Aniline Compounds; D007147:Immunoglobulin Light Chains; D011228:Prealbumin; D019275:Radiopharmaceuticals; D000685:Serum Amyloid A Protein; D013844:Thiazoles; D014020:Tissue Extracts; D014316:Tritium