Syntheses of Functionalized Indium Porphyrins for Monoclonal Antibody Labeling

Abstract

The syntheses and characterizations of five differently hydrosoluble monosubstituted aryl porphyrins are reported. Their metallation with indium-111 was achieved and provided tracers with strong specific activities. The covalent coupling between indium-111 porphyrins and BSA served as a model reaction for the definition of the best experimental coupling conditions; the transposition to the labeling of anti-CEA monoclonal antibody was realized. The conjugates exhibited an in vitro good mAb-labeling efficiency, as well as a good preservation of immunoreactivity.

Synthesis of Porphyrinoids, BODIPYs, and (Dipyrrinato)ruthenium(II) Complexes from Prefunctionalized Dipyrromethanes

“…[33,45,46] Apart from some preliminary work related to the 5-(4-fluoro-3-nitrophenyl)dipyrromethene carried out in our group, [46] to the best of our knowledge only one publication has appeared on the S N Ar of 4-fluoro-3-nitrophenyl-substituted BODIPYs. The 4-fluoro-3-nitrophenyl group has received little attention as a substituent in BODIPYs and porphyrinoids.…”

“…Only a few reports incorporating a 4-fluoro-3-nitrophenyl group as part of BODIPYs and porphyrins have appeared. [33,45,46] Apart from some preliminary work related to the 5-(4-fluoro-3-nitrophenyl)dipyrromethene carried out in our group, [46] to the best of our knowledge only one publication has appeared on the S N Ar of 4-fluoro-3-nitrophenyl-substituted BODIPYs. Volkova and co-workers carried out substitutions on the 4-fluoro-3-nitrophenyl group of a BODIPY with amines and cyclic polyamines, however, this procedure required using quite harsh reaction conditions.…”

Porphyrinoid biohybrid materials as an emerging toolbox for biomedical light management

“…151 On these bases, in 1996, Pereyre and co-workers described the synthesis of radioactive In(III)Por, and their conjugation to BSA bearing anticarcinoembryonic MAb (anti-CEA). 152 After that, Kuroki and co-workers published the bioconjugation of a MAb against CEA, F11-39, to a Ga(III)Por-based PS, by converting the PS carboxyl groups into succinimidyl esters. 153 The authors evaluated the cytotoxic effect of the conjugate in combination with sonodynamic therapy (SDT), which uses ultrasound irradiation, against CEAexpressing human gastric cells, obtaining much better results when applying SDT than with just visible light irradiation.…”

Radiolabelled porphyrins in nuclear medicine

“…To similar ends, radiolabelled porphyrins have been functionalized with biologically relevant entities such as antibodies, antibody fragments, peptides and proteins. Chelators such as porphyrins that bind radiometals with high stability under physiological conditions are ideal for radioimmunoimaging where it is essential to ensure high‐target specificity by minimizing transcomplexation of the radiometal over the extended in vivo accumulation times necessary for antibody targeting . Bedel‐Cloutour et al .…”

“…Chelators such as porphyrins that bind radiometals with high stability under physiological conditions are ideal for radioimmunoimaging where it is essential to ensure high-target specificity by minimizing transcomplexation of the radiometal over the extended in vivo accumulation times necessary for antibody targeting. 70 Bedel-Cloutour et al labelled several monoclonal Immunoglobulin G antibodies and fragment antigen binding species with indium-labelled tritoyl substituted porphyrins using activated esters. 71 Up to 10 molecules of radiotracer were attached to the monoclonal antibodies and 1.5 for antibody fragments.…”