The cholecystokinin-2 receptor (CCK-2R) is overexpressed in several human cancers but displays limited expression in normal tissues. For this reason, it is a suitable target for developing specific radiotracers. In this study, a nastorazepide-based ligand functionalized with a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator (IP-001) was synthesized and labelled with indium-111. The radiolabeling process yielded >95% with a molar activity of 10 MBq/nmol and a radiochemical purity of >98%. Stability studies have shown a remarkable resistance to degradation (>93%) within 120 h of incubation in human blood. The in vitro uptake of [In-111]In-IP-001 was assessed for up to 24 h on a high CCK-2R-expressing tumor cell line (A549) showing maximal accumulation after 4 h of incubation. Biodistribution and single photon emission tomography (SPECT)/CT imaging were evaluated on BALB/c nude mice bearing A549 xenograft tumors. Implanted tumors could be clearly visualized after only 4 h post injection (2.36 +/- 0.26% ID/cc), although a high amount of radiotracer was also found in the liver, kidneys, and spleen (8.25 +/- 2.21%, 6.99 +/- 0.97%, and 3.88 +/- 0.36% ID/cc, respectively). Clearance was slow by both hepatobiliary and renal excretion. Tumor retention persisted for up to 24 h, with the tumor to organs ratio increasing over-time and ending with a tumor uptake (1.52 +/- 0.71% ID/cc) comparable to liver and kidneys.

Preliminary Study of a 1,5-Benzodiazepine-Derivative Labelled with Indium-111 for CCK-2 Receptor Targeting

giovanni marzaro;
2021-01-01

Abstract

The cholecystokinin-2 receptor (CCK-2R) is overexpressed in several human cancers but displays limited expression in normal tissues. For this reason, it is a suitable target for developing specific radiotracers. In this study, a nastorazepide-based ligand functionalized with a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator (IP-001) was synthesized and labelled with indium-111. The radiolabeling process yielded >95% with a molar activity of 10 MBq/nmol and a radiochemical purity of >98%. Stability studies have shown a remarkable resistance to degradation (>93%) within 120 h of incubation in human blood. The in vitro uptake of [In-111]In-IP-001 was assessed for up to 24 h on a high CCK-2R-expressing tumor cell line (A549) showing maximal accumulation after 4 h of incubation. Biodistribution and single photon emission tomography (SPECT)/CT imaging were evaluated on BALB/c nude mice bearing A549 xenograft tumors. Implanted tumors could be clearly visualized after only 4 h post injection (2.36 +/- 0.26% ID/cc), although a high amount of radiotracer was also found in the liver, kidneys, and spleen (8.25 +/- 2.21%, 6.99 +/- 0.97%, and 3.88 +/- 0.36% ID/cc, respectively). Clearance was slow by both hepatobiliary and renal excretion. Tumor retention persisted for up to 24 h, with the tumor to organs ratio increasing over-time and ending with a tumor uptake (1.52 +/- 0.71% ID/cc) comparable to liver and kidneys.
2021
cholecystokinin-2 receptor
indium-111 labelling
nastorazepide
radiopharmaceuticals
File in questo prodotto:
File Dimensione Formato  
molecules-26-00918-s001 (1).pdf

accesso aperto

Descrizione: supporting information
Tipologia: Altro materiale allegato
Licenza: Dominio pubblico
Dimensione 703.24 kB
Formato Adobe PDF
703.24 kB Adobe PDF Visualizza/Apri
molecules-26-00918-v2 (4).pdf

accesso aperto

Descrizione: main text
Tipologia: Versione dell'editore
Licenza: Dominio pubblico
Dimensione 4.49 MB
Formato Adobe PDF
4.49 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/1146052
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 13
  • ???jsp.display-item.citation.isi??? 11
social impact