Evaluation and comparison of a new DOTA and DTPA-bombesin agonist in vitro and in vivo in low and high GRPR expressing prostate and breast tumor models

Priscilla B Pujatti; Julie M Foster; Ciara Finucane; Chantelle D Hudson; Jerome C Burnet; Kerly F M Pasqualoto; Jair Mengatti; Stephen J Mather; Elaine B de Araújo; Jane K Sosabowski

doi:10.1016/j.apradiso.2014.11.006

Evaluation and comparison of a new DOTA and DTPA-bombesin agonist in vitro and in vivo in low and high GRPR expressing prostate and breast tumor models

Appl Radiat Isot. 2015 Feb:96:91-101. doi: 10.1016/j.apradiso.2014.11.006. Epub 2014 Nov 11.

Affiliations

¹ Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, United Kingdom; Nuclear and Energy Research Institute (IPEN), University of Sao Paulo, Sao Paulo, Brazil. Electronic address: [email protected].
² Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, United Kingdom.
³ InviCRO LLC, 27 Drydock Ave, Boston, MA 02210, United States.
⁴ Biospace Lab, 13 rue Georges Auric, 75011 Paris, France.
⁵ Laboratory of Biochemistry and Biphysics, Butantan Institute, Sao Paulo, Brazil.
⁶ Nuclear and Energy Research Institute (IPEN), University of Sao Paulo, Sao Paulo, Brazil.

PMID: 25479439
DOI: 10.1016/j.apradiso.2014.11.006

Abstract

We evaluated and compared a new bombesin analog [Tyr-Gly5, Nle(14)]-BBN(6-14) conjugated to DOTA or DTPA and radiolabeled with In-111 in low and high GRPR expressing tumor models. Both peptides were radiolabeled with high radiochemical purity and specific activity. In vitro assays on T-47D, LNCaP and PC-3 cells showed that the affinity of peptides is similar and a higher binding and internalization of DOTA-peptide to PC-3 cells was observed. Both peptides could target PC-3 and LNCaP tumors in vivo and both tumor types could be visualized by microSPECT/CT.

Keywords: Bombesin; Comparison; DOTA; DTPA; GRPR.

Publication types

Comparative Study
Evaluation Study
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bombesin / analogs & derivatives*
Bombesin / chemistry
Breast Neoplasms / diagnostic imaging*
Breast Neoplasms / metabolism*
Cell Line, Tumor
Drug Stability
Female
Heterocyclic Compounds, 1-Ring*
Heterografts
Humans
In Vitro Techniques
Indium Radioisotopes
Male
Mice, SCID
Neoplasm Transplantation
Pentetic Acid / analogs & derivatives*
Prostatic Neoplasms / diagnostic imaging*
Prostatic Neoplasms / metabolism*
Radionuclide Imaging
Radiopharmaceuticals* / chemistry
Receptors, Bombesin / metabolism*
Tissue Distribution

Substances

Heterocyclic Compounds, 1-Ring
Indium Radioisotopes
Radiopharmaceuticals
Receptors, Bombesin
1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
Pentetic Acid
Bombesin