0000000001001042
AUTHOR
Jean-philippe Sinnes
Synthesis, Labeling and Preclinical Evaluation of a Squaric Acid Containing PSMA Inhibitor Labeled with 68 Ga: A Comparison with PSMA‐11 and PSMA‐617
The L-lysine urea-L-glutamate (KuE) represents a key motif in recent diagnostic and therapeutic radiopharmaceuticals targeting the prostate specific membrane antigen (PSMA). Using a squaric acid moiety for coupling of KuE with a radioactive label, the squaric acid as a linker in the PSMA ligand seems to mimic the aromatic structure of the naphthylalanine unit on PSMA-617. In this work, we investigate the influence of squaric acid moiety on the biological activity of the compound carrying a KuE motif and three typical chelates. The derivatives TRAM.SA.KuE, DOTAGA.SA.KuE and NODAGA.SA.KuE were all synthesized in straightforward organic reactions and purified by HPLC afterward. Different amoun…
Evaluation of the inverse electron demand Diels-Alder reaction in rats using a scandium-44-labelled tetrazine for pretargeted PET imaging
Background Pretargeted imaging allows the use of short-lived radionuclides when imaging the accumulation of slow clearing targeting agents such as antibodies. The biotin-(strept)avidin and the bispecific antibody-hapten interactions have been applied in clinical pretargeting studies; unfortunately, these systems led to immunogenic responses in patients. The inverse electron demand Diels-Alder (IEDDA) reaction between a radiolabelled tetrazine (Tz) and a trans-cyclooctene (TCO)-functionalized targeting vector is a promising alternative for clinical pretargeted imaging due to its fast reaction kinetics. This strategy was first applied in nuclear medicine using an 111In-labelled Tz to image TC…
Instant kit preparation of 68Ga-radiopharmaceuticals via the hybrid chelator DATA: clinical translation of [68Ga]Ga-DATA-TOC
Purpose The widespread use of 68Ga for positron emission tomography (PET) relies on the development of radiopharmaceutical precursors that can be radiolabelled and dispensed in a simple, quick, and convenient manner. The DATA (6-amino-1,4-diazapine-triacetate) scaffold represents a novel hybrid chelator architecture possessing both cyclic and acyclic character that may allow for facile access to 68Ga-labelled tracers in the clinic. We report the first bifunctional DATA chelator conjugated to [Tyr3]octreotide (TOC), a somatostatin subtype 2 receptor (SST2)-targeting vector for imaging and functional characterisation of SSTR2 expressing tumours. Methods The radiopharmaceutical precursor, DATA…
Novel bifunctional DATA chelator for quick access to site-directed PET 68Ga-radiotracers: preclinical proof-of-principle with [Tyr3]octreotide
Molecular imaging of tumors with the PET radionuclide 68Ga has gained momentum in clinical oncology due to the expanding availability of commercial 68Ge/68Ga-generators in combination with state-of-the-art PET/CT and PET/MRI hybrid imaging systems. Concurrently, interesting peptide-based or small-size vectors have been developed for theranostic use in cancer patients. Owing to the short half-life of 68Ga (t1/2 = 67.7 min) and the sensitivity of many targeting biomolecules, labeling and kit reconstitution in mild conditions allowing for quick access to ready-for-injection PET-tracers are highly desirable. The novel DATA ((6-pentanoic acid)-6-(amino)methy-1,4-diazepinetriacetate) chelator pre…
Additional file 1: of Evaluation of the inverse electron demand Diels-Alder reaction in rats using a scandium-44-labelled tetrazine for pretargeted PET imaging
Figure S1. HPLC radiochromatogram chromatogram of [44Sc]3 (Rt = 5.7 min). Figure S2. In vitro stability of [44Sc]3. (A) radio-TLC analysis of [44Sc]3 with 2 (lane 2) and without 2 (lane 1) following radiosynthesis. (B) Percent intact over time after incubation in saline (red circles) and human serum albumin (blue squares) for 0.5–24 h at 37 °C. Table S1. Summary of the uptake for [44Sc]3 in Wistar rats. Table S2. Summary of bone uptake values (4 h p.i.) and TCO:Tz ratios in individual rats. (DOC 275 kb)
Additional file 1: of Instant kit preparation of 68Ga-radiopharmaceuticals via the hybrid chelator DATA: clinical translation of [68Ga]Ga-DATA-TOC
Table S1. Binding affinities of [natGa]Ga-DATA-TOC and [natGa]Ga-DOTA-TOC on hSST2/3/5, as determined during displacement of [125I-Tyr25]LTT-SS28 from transfected HEK293-hSST2/3/5 cell membranes; LTT-SS28 served as reference. Table S2. Uptake in terms of %IA of [68Ga]Ga-DATA-TOC or [68Ga]Ga-DOTA-TOC in selected organs of MPC-mCherry tumour-bearing female NMRI nu/nu mice 1 h p.i. (218 ± 57 MBq (11.2 nmol peptide/kg) and 441 ± 109 MBq (10.5 nmol peptide)/kg body weight, respectively; blocking after coinjection of 100 µg/mouse [Nal3]octreotide acetate)). Table S3. Radioactivity concentration in terms of SUV of [68Ga]Ga-DATA-TOC or [68Ga]Ga-DOTA-TOC in selected organs of MPC-mCherry tumour-bear…