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.

Comparison of the tolerability of Tb- and Lu-labeled somatostatin analogues in the preclinical setting.

Purpose: [Lu]Lu-DOTATATE is an established somatostatin receptor (SSTR) agonist for the treatment of metastasized neuroendocrine neoplasms, while the SSTR antagonist [Lu]Lu-DOTA-LM3 has only scarcely been employed in clinics. Impressive preclinical data obtained with [Tb]Tb-DOTA-LM3 in tumor-bearing mice indicated the potential of terbium-161 as an alternative to lutetium-177. The aim of the present study was to compare the tolerability of Tb- and Lu-based DOTA-LM3 and DOTATATE in immunocompetent mice.

Terbium-149 production: a focus on yield and quality improvement towards preclinical application.

Terbium-149 (T = 4.1 h, E = 3.98 MeV (16.

Investigations Using Albumin Binders to Modify the Tissue Distribution Profile of Radiopharmaceuticals Exemplified with Folate Radioconjugates.

Introducing an albumin-binding entity into otherwise short-lived radiopharmaceuticals can be an effective means to improve their pharmacokinetic properties due to enhanced blood residence time. In the current study, DOTA-derivatized albumin binders based on 4-(-iodophenyl)butanoate (DOTA-ALB-1 and DOTA-ALB-3) and 5-(-iodophenyl)pentanoate entities (DOTA-ALB-24 and DOTA-ALB-25) without and with a hydrophobic 4-(aminomethyl)benzoic acid (AMBA) linker unit, respectively, were synthesized and labeled with lutetium-177 for in vitro and in vivo comparison. Overall, [Lu]Lu-DOTA-ALB-1 demonstrated ~3-fold stronger in vitro albumin-binding affinity and a longer blood residence time (T ~8 h) than [Lu]Lu-DOTA-ALB-24 (T ~0.