68Ga-Labeled Bombesin Analogs for Receptor-Mediated Imaging

  • Raunak Varshney
  • Puja P. Hazari
  • P. Fernandez
  • J. Schulz
  • M. Allard
  • Anil  K. Mishra
Conference paper
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 194)

Abstract

Targeted receptor-mediated imaging techniques have become crucial tools in present targeted diagnosis and radiotherapy as they provide accurate and specific diagnosis of disease information. Peptide-based pharmaceuticals are gaining popularity, and there has been vast interest in developing 68Ga-labeled bombesin (Bn) analogs. The gastrin-releasing peptide (GRP) family and its Bn analog have been implicated in the biology of several human cancers. The three bombesin receptors GRP, NMB, and BRS-3 receptor are most frequently ectopically expressed by common, important malignancies. The low expression of Bn/GRP receptors in normal tissue and relatively high expression in a variety of human tumors can be of biological importance and form a molecular basis for Bn/GRP receptor-mediated imaging. To develop a Bn-like peptide with favorable tumor targeting and pharmacokinetic characteristics for possible clinical use, several modifications in the Bn-like peptides, such as the use of a variety of chelating agents, i.e., acyclic and macrocyclic agents with different spacer groups and with different metal ions (gallium), have been performed in recent years without significant disturbance of the vital binding scaffold. The favorable physical properties of 68Ga, i.e., short half-life, and the fast localization of small peptides make this an ideal combination to study receptor-mediated imaging in patients.

Keywords

Positron Emission Tomography Positron Emission Tomography Imaging Bifunctional Chelate Bombesin Receptor Fast Blood Clearance 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

Ac

Acetyl

Aca

Aminohexanoic acid

ACMpip

4-Aminocarboxymethylpiperidine

AMBA

Aminobenzoyl

Bn/BBN

Bombesin

BRS-3

Bombesin receptor subtype 3

Bzdig

p-aminobenzyldiglycolic acid

BZH3

[DTyr6,βAla11,Thi13,Nle14]Bn(6–14)

Cha

Cyclohexylalanine

DOTA

1,4,7,10-Triazacyclododecanetetraacetic acid

DTPA

Diethylenetriaminepentaacetic acid

Des-Met

Methionine removed

FA01010

(4R,5S)-4-Amino-5-methylheptanoic acid

GRP

Gastrin-releasing peptide

GRP-R/GRPR

Gastrin-releasing peptide receptor

GPR-R/GPRR

G-protein receptor

Ga

Gallium

GI

Gastrointestinal

mIP

meta-phenylalanine

MBq

Megabecquerel

NHEt

Et = ethyl

NMB

Neuromedin B

NMBR

Neuromedin B receptor

NOTA

1,4,7-Triazacyclononanetriacetic acid

PEG2

(2-Aminoethyl)-carboxymethyl ether

PEG4

15-Amino-4,7,10,13-tetraoxapentadecanoic acid

PET

Positron emission tomography

RM1

H-DPhe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2

RGD

(Arginine-glycine-aspartic acid)

SPECT

Single-photon emission computed tomography

Sta

Statine: (3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid

Tha

β-(2-Thienyl) alanine

Thi

3-(2-Thienyl) alanine

Tpi

2,3,4,9-Tetrahydro-1H-pyridol[3,4-b]indol-3-carboxylic acid

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Raunak Varshney
    • 1
  • Puja P. Hazari
    • 1
  • P. Fernandez
    • 2
  • J. Schulz
    • 2
  • M. Allard
    • 2
  • Anil  K. Mishra
    • 1
  1. 1.DCRSINMAS, DRDODelhiIndia
  2. 2.University of Bordeaux, CNRS, INCIATalenceFrance

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