Utilize este identificador para referenciar este registo: https://hdl.handle.net/10316/12871
Título: NODAGATOC, a New Chelator-Coupled Somatostatin Analogue Labeled with [67/68Ga] and [111In] for SPECT, PET, and Targeted Therapeutic Applications of Somatostatin Receptor (hsst2) Expressing Tumors
Autor: Eisenwiener, Klaus-Peter 
Prata, M. I. M. 
Buschmann, I. 
Zhang, Han-Wen 
Santos, A. C. 
Wenger, Sandra 
Reubi, Jean Claude 
Mäcke, Helmut R. 
Data: Mai-2002
Editora: American Chemical Society
Citação: Bioconjugate Chemistry. 13:3 (2002) 530-541
Resumo: A monoreactive NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid) derived prochelator (1-(1-carboxy-3-carbo-tert-butoxypropyl)-4,7-(carbo-tert-butoxymethyl)-1,4,7-triazacyclononane (NODAGA(tBu)3)) was synthesized in five steps with an overall yield of 21%. It is useful for the coupling to the N-terminus of peptides on solid phase and in solution; it was coupled to [Tyr3]-octreotide (TOC) on solid phase, and the resulting peptide, NODAGA-Tyr3-octreotide (NODAGATOC), was labeled with the radiometals 111In and 67Ga in high yields and good specific activities. [67Ga]− and [111In]−NODAGA-Tyr3-octreotide appear to be useful to visualize primary tumors and metastases which express somatostatin receptors subtype 2 (sstr2), such as neuroendocrine tumors, because of their high affinity to this receptor subtype with IC50 = 3.5 ± 1.6 nM and 1.7 ± 0.2 nM, respectively. NODAGATOC could be used as a SPECT and PET tracer, when labeled with 111In, 67Ga, or 68Ga, and even for therapeutic applications. Surprisingly, [111In]−NODAGATOC shows 2 times higher binding affinity to sstr2, but also a factor of 4 higher affinity to sstr5 compared to [67Ga]−NODAGATOC. [67Ga]−NODAGATOC is very stable in serum and rat liver homogenate. There is no difference in the rate of internalization into AR4-2J rat pancreatic tumor cells; both radioligands are highly internalized, at 4 h a 3 times higher uptake compared to [111In]−DOTA-Tyr3-octreotide ([111In]−DOTATOC) was found. The biodistribution of [67Ga]−NODAGATOC in AR4-2J tumor bearing nude mice is very favorable at short times after injection; there is fast excretion from all nontarget organs except the kidneys and high uptake in sst receptor rich organs and in the AR4-2J tumor. Again it is superior to [111In]−DOTATOC in this respect. The results indicate an improved biological behavior which is likely due to the fact that an additional spacer group separates the chelate from the pharmacophoric part of the somatostatin analogue
URI: https://hdl.handle.net/10316/12871
ISSN: 1043-1802
Direitos: openAccess
Aparece nas coleções:FMUC Medicina - Artigos em Revistas Internacionais
FCTUC Ciências da Vida - Artigos em Revistas Internacionais

Ficheiros deste registo:
Ficheiro Descrição TamanhoFormato
NODAGATOC, a New Chelator-Coupled Somatostatin Analogue.pdf138.74 kBAdobe PDFVer/Abrir
Mostrar registo em formato completo

Visualizações de página

289
Visto em 26/mar/2024

Downloads

461
Visto em 26/mar/2024

Google ScholarTM

Verificar


Todos os registos no repositório estão protegidos por leis de copyright, com todos os direitos reservados.