Preclinical investigation of [Tb]Tb-DOTATATE and [Tb]Tb-DOTA-LM3 for tumor-targeted alpha therapy.

Purpose: Terbium-149 is a short-lived α-particle emitter, potentially useful for tumor-targeted therapy. The aim of this study was to investigate terbium-149 in combination with the somatostatin receptor (SSTR) agonist DOTATATE and the SSTR antagonist DOTA-LM3. The radiopeptides were evaluated to compare their therapeutic efficacy in vitro and in vivo.

Preclinical comparison of (radio)lanthanides using mass spectrometry and nuclear imaging techniques: biodistribution of lanthanide-based tumor-targeting agents and lanthanides in ionic form.

Purpose: With the growing interest in exploring radiolanthanides for nuclear medicine applications, the question arises as to whether they are generally interchangeable without affecting a biomolecule's pharmacokinetic properties. The goal of this study was to investigate similarities and differences of four (radio)lanthanides simultaneously applied as complexes of biomolecules or in ionic form.

Methods: Inductively coupled plasma mass spectrometry (ICP-MS) was employed for the simultaneous detection of four lanthanides (Ln = lutetium, terbium, gadolinium and europium) in biological samples.

Exploration of (R)-[C]YH168 as a PET tracer for imaging monoacylglycerol lipase in the brain: from mice to non-human primates.

Purpose: The monoacylglycerol lipase (MAGL) plays a pivotal role in modulating the endocannabinoid system and is considered an attractive therapeutic target for diseases in both the central nervous system and periphery. The current study aimed to develop and evaluate a suitable carbon-11 labeled tracer for imaging MAGL in preclinical studies.

Methods: (R)-YH168 was synthesized via a multi-step pathway and its half-maximal inhibitory concentration (IC) values were measured using an enzymatic assay.

Site-Specific Modification of Native IgGs with Flexible Drug-Load.

Homogeneous, site-specifically conjugated antibodies have shown to result in antibody-drug conjugates (ADCs) with improved efficacy and tolerability compared to stochastically conjugated ADCs. However, precisely controlling the drug load as well as attaching multiple payload moieties to the antibody remains challenging. Here, we demonstrate the simple and direct modification of native IgG-antibodies at the residue glutamine 295 (Q295) without the need for any protein engineering with flexible drug-to-antibody ratios of one or multiple payloads.