Frontispiece: Photochemical Conjugation and One‐Pot Radiolabelling of Antibodies for Immuno‐PET

Synthesis and Photochemical Studies on Gallium and Indium Complexes of DTPA-PEG3-ArN3 for Radiolabeling Antibodies

“…[9][10][11] However, there are only a few examples whereby photochemical conjugation was used in the synthesis of radiotracers. [12][13][14][15][16][17][18][19][20][21] Recently, our group demonstrated that photoradiochemical conjugation methods using different photoactive macrocyclic and acyclic chelates suitable for complexation of gallium, copper or zirconium radionuclides can be successfully coupled to proteins via light-induced activation of an aryl azide (ArN3) group. Photoradiosynthesis was completed in ~10 min starting directly from fully formulated antibody solutions (avoiding pre-purification and buffer exchange of the antibody), in high radiochemical yields (up to ~75%), and without compromising the structural integrity or biological viability of the protein.…”

“…Photoradiosynthesis was completed in ~10 min starting directly from fully formulated antibody solutions (avoiding pre-purification and buffer exchange of the antibody), in high radiochemical yields (up to ~75%), and without compromising the structural integrity or biological viability of the protein. [18][19][20][21] However, a current restriction is that all reported photoactive chelates are limited to a maximum of 6 donor atoms which makes them unsuitable for coordination chemistry using larger metal ions like In 3+ that preferentially form complexes with higher coordination numbers.…”

Photoactive chelates for radiolabelling proteins

“…Our previous work found that photoradiochemical labelling does not compromise the biological activity (immunoreactivity) of the antibody. [18] In summary, experiments showed that photoactive derivatives of widely used aza-macrocyclic chelates (NOTA, DOTA and DOTAGA) are suitable for photochemical radiolabelling of proteins. Introduction of these photoactive chelates opens the possibility of using photoradiochemical methods with a broad range of radionuclides taken from across the periodic table.…”

“…[7][8][9][10][11][12][13][14][15][16][17] We recently demonstrated that a one-pot, photoradiochemical process involving 68 Ga-radiolabelling of a macrocyclic chelate and photochemical conjugation with proteins in situ facilitates the direct synthesis, purification and formulation of 68 Galabelled mAbs in <20 min. [18] In efforts to expand the radiochemical scope of this photoradiochemical approach, here we report the synthesis, characterisation and 68 Garadiochemistry of three new photoreactive chelates derived from the aza-macrocycles NOTA, DOTA and DOTAGA. These chelates offer different numbers of donor groups, cavity sizes, and overall charges that can be tuned for coordination of radioactive metal ions (with formal oxidation states of +2, +3, +4 or +5) from across p-, d-and f-blocks.…”

“…In all cases, semi-preparative HPLC was used to isolate the compounds in high purity. Compound 1 was synthesised in 37% yield after the N-hydroxysuccinimide activated ester (NOTA-NHS) was reacted with a pre-synthesised [18] polyethylene glycol (PEG)-functionalised ArN 3 reagent (N 3 -PEG 3 -NH 2 , Figure 2 [green trace] and Supporting Information Figures S1 -S6). Compound 3 was synthesised in 89% yield via the reaction of DOTA-PEG 4 -NH 2 with the activated NHS ester, 2,5dioxopyrrolidin-1-yl-4-azidobenzoate (2, Figures S7 -S14).…”