Strategic Evaluation of the Traceless Staudinger Ligation for Radiolabeling with the Tricarbonyl Core

Abstract

The traceless Staudinger ligation with its two variants is a powerful biorthogonal conjugation method not only for the connection of biomolecules, but also for the introduction of fluorescence- or radiolabels under mild reaction conditions. Herein, the strategic evaluation of the traceless Staudinger ligation for radiolabeling 99mTc using the fac-[Tc(CO)3]+ core is presented. A convenient and high-yielding three-step synthetic procedure of dipicolylamine-based phosphanols as ligands for the mild radiolabeling was developed. The labeling was accomplished using a tricarbonyl kit and a 99mTc-pertechnetate generator eluate showing 87% radiochemical conversion. The respective rhenium-based, non-radioactive reference compounds were synthesized using (Et4N)2[Re(CO)3Br3] as precursor. All products were analyzed by NMR, MS, and elemental analysis. Additional XRD analyses were performed.

Copper-free click bioconjugation of technetium-99m complexes using strained cyclononyne derivatives

“…The tricarbonyl kits were prepared in-house as reported elsewhere. 35,40 N-(3-((3-Bromopropyl)sulfonamido)propyl)-2-nitrobenzenesulfonamide 3. Et 3 N (4.45 g, 44.0 mmol, 5.00 eq.)…”

“…Both new tridentate chelators are based on the 2,2′-dipicolylamine (DPA) moiety, which is proven to be an effective ligand for the stable coordination of 99m Tc in the oxidation state +1. [33][34][35] The design of the novel chelator for Cu-free click-labelling is based on the diazacyclononyne (DACN) heterocycle. It was recently introduced for SPAAC by Kawasaki et al 36,37 and is easily accessible via a convenient one-pot double Nicholas reaction.…”

“…For radiolabelling using the 99m Tc-tricabonyl approach, fac-[ 99m Tc][Tc(CO) 3 (H 2 O) 3 ] + was prepared as the starting complex with the tricarbonyl kit as reported earlier 35,40 with an RCC of >99% by adding [ 99m Tc]TcO 4 − (1 mL, 1-1.5 GBq) eluted from a 99 Mo/ 99m Tc generator with 0.9% saline to the kit followed by heating to 100 °C for 20 min. fac-[[ 99m Tc]Tc(CO) 3 (H 2 O) 3 ] + with t R = 13.7 min was used without purification for all ensuing radiolabelling procedures (see the ESI †).…”

Monomeric and dimeric complexes of pyrimidine-4,6-dicarboxylic acid with organometallic fac-[M(CO)3]+ (M = Re and 99mTc) core as radiopharmaceutical probes

“…In addition, the possibility of combining radiometal agents with cytotoxicity and imaging properties gave rise to a new concept of molecule-based theranostic radiopharmaceuticals with a speci c amount of therapeutic and imaging agents [17]. In this way, the existence of similar coordination chemistry between Re and Tc makes possible to afford stable heterodinuclear 99m Tc/ 186/188 Re complexes with 99m Tc and 186/188 Re showing similar electronic properties, and such complexes act as theranostic radiopharmaceuticals displaying imaging and therapeutic properties [45]. Therefore, heterodinuclear 99m Tc/Re complex [(µpmdc) 2 (Re(CO) 3 )( 99m Tc(CO) 3 )] 2− (5) reported in this study will be a model for future design of theranostic radiopharmaceuticals combining imaging and therapy.…”

Recent Advances in Bioorthogonal Click Chemistry for Enhanced PET and SPECT Radiochemistry

“…(3) 18 F-Labeled tetrazine products, such as [ 18 F]­SiFA-OTz and [ 18 F]­F-Tz (used in IEDDA chemistry, Figure C). (4) Other radioligands (used in traceless SLR or a novel click reaction; Figure D) were also examined for the development of imaging agents as part of the pretargeting strategy. − …”