Preparation and stability of ethanol‐free solution of [¹⁸F]florbetapir ([¹⁸F]AV‐45) for positron emission tomography amyloid imaging

Abstract

We have developed an ethanol-free formulation method of [(18) F]florbetapir ([(1) (8) F]AV-45) using a commercially available automated JFE multi-purpose synthesizer. We have also evaluated the radiochemical stability in an ethanol-free solution of [(18) F]AV-45 under visible light irradiation and dark conditions by comparison with a conventional 10% ethanol solution of [(18) F]AV-45. [(18) F]AV-45 was obtained with a radiochemical yield of 55.1 ± 2.2% (decay-corrected to end of bombardment), specific activity of 591.6 ± 90.3 GBq/µmol and radiochemical purity of >99% within a total synthesis time of about 73 min. The radiochemical purity of [(18) F]AV-45 formulated by dissolving the ethanol-free solution was found to decrease as a function of the period of exposure to visible light. In contrast, the visible light photolysis could be suppressed by adding 10% ethanol to the formulation or by avoiding exposure to visible light. In the radiosynthesis of [(18) F]AV-45 formulated by dissolving the ethanol-free solution, [(18) F]AV-45 could be obtained with high radiochemical purity and high stability by avoiding exposure to visible light.

Applications of Fluorine in Medicinal Chemistry

“…146 The synthesis of 269 involves a two-step process in which the tosyl group of 268 is displaced by [ 18 F]-flouride at elevated temperature using K.2.2.2/[ 18 F]KF followed by removal of the Boc protecting group. 147 Improved methods for aliphatic nucleophilic fluorination with [ 18 F]-fluoride include the use of microwave, ionic liquids, the inclusion of tertiary alcohols, and the use of fluorous solid-phase methods that allows rapid purification of [ 18 F]labeled products. 148 The enantioslective preparation of [ 18 F]-fluorohydrins, via epoxide ring opening using the chiral catalysts [ F]-fluoride using standard K.2.2.2 conditions (Scheme 3a).…”

“…[ 18 F]-Florbetapir is the first Food and Drug Administration (FDA) approved PET tracer for quantifying amyloid plaque burden in humans during therapy or as a patient enrichment biomarker for designing more effective clinical trials . The synthesis of 269 involves a two-step process in which the tosyl group of 268 is displaced by [ 18 F]-flouride at elevated temperature using K.2.2.2/[ 18 F]­KF followed by removal of the Boc protecting group . Improved methods for aliphatic nucleophilic fluorination with [ 18 F]-fluoride include the use of microwave, ionic liquids, the inclusion of tertiary alcohols, and the use of fluorous solid-phase methods that allows rapid purification of [ 18 F]-labeled products …”

Optimization of Automatic Synthesis and Separation of [18F] AV-45 and Quality Control

“…There was a waiting time for confirmation between each step of synthesis. The time from the beginning of synthesis to obtaining the final product was about 60 min, which is unfortunately long ( Yao et al, 2010 ; Hayashi et al, 2013 ; Li et al, 2016 ).…”

An improved preparation of [18F]AV‐45 by simplified solid‐phase extraction purification

“…Amyloid‐β plaques in the brain are associated with mild cognitive impairment or dementia of uncertain etiology . The original method for preparing [ 18 F]AV‐45 ([ 18 F] 5 ) was based on the final HPLC purification . Similar to the [ 18 F]FDG production described above, we previously reported an effort to streamline the [ 18 F]AV‐45 ([ 18 F] 5 ) production .…”

“…11,12 The original method for preparing [ 18 F]AV-45 ([ 18 F]5) was based on the final HPLC purification. 13,14 Similar to the [ 18 F]FDG production described above, we previously reported an effort to streamline the [ 18 F]AV-45 ([ 18 F]5) production. [15][16][17] We wish to develop a routine production method, which would be amendable for radiopharmacy operation.…”