Studies into radiolytic decomposition of fluorine-18 labeled radiopharmaceuticals for positron emission tomography

Abstract

Radiolytic decomposition of high specific concentration radiopharmaceuticals is an undesired side-effect that can hamper development of novel PET tracers. This was particularly evident in a series of carbon-11 and fluorine-18 labeled mono- and dimethyl-substituted aryl amines, where rapid decomposition was observed in isolation and formulation steps. We tested a number of additives that inhibit radiolysis and can be safely added to the synthesis procedures (purification and isolation) and reformulation steps to provide suitable clinical formulations. Ethanol and sodium ascorbate are established anti-oxidant stabilizers that completely inhibit radiolytic decomposition and are amenable to human use. Herein, we also demonstrate for the first time that nitrones are non-toxic radical scavengers that are capable of inhibiting radiolysis.

General Method for the 11C‐Labeling of 2‐Arylpropionic Acids and Their Esters: Construction of a PET Tracer Library for a Study of Biological Events Involved in COXs Expression

“…The addition of ascorbic acid as an antioxidant stabilizer to the reaction mixture before the HPLC purification also effectively prevented the radiolysis. [19] Consequently, we found that the six kinds of 2-aryl- 11 C]2 in class C were very unstable, and they required not only ascorbic acid but also synthetic conditions with the lower radioactivity (~15 GBq). The reaction with higher radioactivity (> 15 GBq) gave many kinds of products among which it was too difficult to isolate the desired labeled compound.…”

An Automated Multidose Synthesis of the Potentiometric PET Probe 4-[18F]Fluorobenzyl-Triphenylphosphonium ([18F]FBnTP)

“…Since numerous publications describe the synthesis of [ 18 F]FBA in RCY ranging from 50 to 72 % [20, 21], we investigated the reason for the low formation of [ 18 F]FBA in our hands. We considered radiolysis of [ 18 F]FBA during SPE purification in the presence of water as a possible reason for low yields from high starting activities [22]. This possibility was explored by synthesizing [ 18 F]FBA with escalating amounts of radioactivity and a negative correlation between starting activities and synthesis yield was indeed observed (Suppl.…”

Pitfalls and Limitations of SPECT, PET, and Therapeutic Radiopharmaceuticals

“…66 Ethanol and ascorbate are among the most effective radioprotectants. Fortuitously, reformulation of products often requires the use of ethanol, which remains in the final product as both a cosolvent and radioprotectant.…”