The next step in increasing the efficacy of PRRT: Preclinical studies in vicvo and in vitro with 213Bi-[DOTA0,Tyr3]-octreotate

Peptide Receptor RadioTherapy shows a reasonable objective response rate of 30-35% with the use of 177Lu-[DOTA0,Tyr3]-octreotate (177Lu-DOTATATE). Alpha-particle emitters can augment the therapeutic efficacy of PRRT and make it exceptional, especially in small tumours and metastasis cell clusters. In preclinical studies with alpha-emitter labeled peptides high specific activity is required, because of the high-affinity, but low-capacity of tumour cell receptors. The stability of -radiopeptides should be maintained until receptor mediated uptake, both in vivo as in vitro , to minimize off-targeting effects. Also the radio-peptide should have rapid uptake ,high retention in tumour tissue and high clearance capacity from normal tissue. In this study we optimized the application of 213Bi-[DOTA0,Tyr3]-octreotate (213Bi-DOTATATE) for TAT in vitro and in vivo. We investigated in various somatostatin receptor-positive tumour models in mice the therapeutic efficacy of 213Bi-DOTATATE. The labelling procedure for 213Bi-DOTATATE was chemically optimized for preclinical applications.

CHAN Ho Sze;  KONIJNENBERG M.W.;  DE BLOIS Erik;  KOELEWIJN S.J.;  ANDERSON Tamara;  NYSUS Monique;  BREEMAN W.A.P.;  ATCHER Robert;  MORGENSTERN Alfred;  BRUCHERTSEIFER Frank;  NORENBERG Jeffrey;  DE JONG Marion; 

2015-11-06

SPRINGER

JRC96963

1619-7070,   

https://publications.jrc.ec.europa.eu/repository/handle/JRC96963,   

10.1007/s00259-015-3198-z,