Radiopharmaceutical formulation and preliminary clinical dosimetry of [Lu]Lu-DOTA-MGS5 for application in peptide receptor radionuclide therapy.

Purpose: Radiolabelled minigastrin (MG) analogues targeting the cholecystokinin-2 receptor (CCK2R) have proven to be a promising approach for peptide receptor radionuclide therapy (PRRT). In this study, we report on the radiopharmaceutical development and standardization of the preparation of [Lu]Lu-DOTA-MGS5 using an automated synthesis module. Furthermore, we present the preclinical tests required to move forward towards a first therapeutic clinical trial as well as preliminary clinical dosimetry data.

[Ga]Ga-FAP-2286-Synthesis, Quality Control and Comparison with [F]FDG PET/CT in a Patient with Suspected Cholangiocellular Carcinoma.

[Ga]Ga-FAP-2286 is a new peptide-based radiopharmaceutical for positron-emission tomography (PET) that targets fibroblast activation protein (FAP). This article describes in detail the automated synthesis of [Ga]Ga-FAP-2286 using a commercially available synthesis tool that includes quality control for routine clinical applications. The synthesis was performed using a Scintomics GRP-3V module and a GMP grade Ge/Ga generator.

Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition.

During neural tube (NT) development, the notochord induces an organizer, the floorplate, which secretes Sonic Hedgehog (SHH) to pattern neural progenitors. Conversely, NT organoids (NTOs) from embryonic stem cells (ESCs) spontaneously form floorplates without the notochord, demonstrating that stem cells can self-organize without embryonic inducers. Here, we investigated floorplate self-organization in clonal mouse NTOs.

Automated production of [Ga]Ga-DOTA-exendin-4 via fractionated radionuclide generator elution on a cassette based synthesis module.

Background: PET/CT imaging of glucagon-like peptide receptor 1 has recently filled a gap in reliably diagnosing insulinoma through non-invasive means. Ga-labelled derivatives of exendin-4 show high sensitivity as well as sufficient serum stability to enable routine clinical application. Here, we provide data for automated production of [Ga][Nle,Lys(Ahx-DOTA-Ga)NH]exendin-4 ([Ga]Ga-DOTA-exendin-4) on a cassette based synthesis module (Modular-Lab PharmTracer, Eckert & Ziegler) using commercially available cassettes in combination with an approved Ge/Ga generator (GalliaPharm, Eckert & Ziegler).

Precision RNAi using synthetic shRNAmir target sites.

Loss-of-function genetic tools are widely applied for validating therapeutic targets, but their utility remains limited by incomplete on- and uncontrolled off-target effects. We describe artificial RNA interference (ARTi) based on synthetic, ultra-potent, off-target-free shRNAs that enable efficient and inducible suppression of any gene upon introduction of a synthetic target sequence into non-coding transcript regions. ARTi establishes a scalable loss-of-function tool with full control over on- and off-target effects.