0000000001290710
AUTHOR
Theodosia Maina
From Bench to Bedside—The Bad Berka Experience With First-in-Human Studies
Precision oncology is being driven by rapid advances in novel diagnostics and therapeutic interventions, with treatments targeted to the needs of individual patients on the basis of genetic, biomarker, phenotypic, or psychosocial characteristics that distinguish a given patient from other patients with similar clinical presentations. Inherent in the theranostics paradigm is the assumption that diagnostic test results can precisely determine whether an individual is likely to benefit from a specific treatment. As part and integral in the current era of precision oncology, theranostics in the context of nuclear medicine aims to identify the appropriate molecular targets in neoplasms (diagnost…
Amide-to-triazole switch vs. in vivo NEP-inhibition approaches to promote radiopeptide targeting of GRPR-positive tumors
Abstract Introduction Radiolabeled bombesin (BBN)-analogs have been proposed for diagnosis and therapy of gastrin-releasing peptide receptor (GRPR)-expressing tumors, such as prostate, breast and lung cancer. Metabolic stability represents a crucial factor for the success of this approach by ensuring sufficient delivery of circulating radioligand to tumor sites. The amide-to-triazole switch on the backbone of DOTA-PEG 4 -[Nle 14 ]BBN(7–14) ( 1 ) was reported to improve the in vitro stability of resulting 177 Lu-radioligands. On the other hand, in-situ inhibition of neutral endopeptidase (NEP) by coinjection of phosphoramidon (PA) was shown to significantly improve the in vivo stability and …
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 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…