The document summarizes a study comparing a new bombesin peptide antagonist (JMV4168) to agonists for targeting gastrin releasing peptide receptors (GRPR) overexpressed on prostate and breast cancers. In vitro assays showed JMV4168 bound primarily to the surface of prostate cancer cells, while agonists were more internalized. In vivo studies in mice found JMV4168 had high tumor uptake and fast clearance from GRPR-rich pancreas and background tissues, indicating its potential as a safer agent than agonists for clinical imaging and therapy of GRPR-overexpressing cancers.

1. A new tumour targeting bombesin peptide: agonist vs antagonist
Linda M. van der Graaf1, Thea Maina2, Pantelis J. Marsouvanidis2, Marleen Melis1, Eric P.
Krenning1, Jean martinez3, Luc Brunel3, Jean-Alain Fehrentz3, Berthold A. Nock2, Marion de Jong1
1 Erasmus MC, dept. of Nuclear Medicine, Rotterdam, the Netherlands, 2 NCSR “Demokritos”, Athens, Greece,
3 Faculté de Pharmacie, CNRS-Universités de Montpellier 1 et 2, Montpellier, France
Introduction: Aim:
In the current study the new bombesin antagonist
radionuclide peptide receptor on tumour cell JMV4168 was characterized, which is an attractive
alternative to agonists (e.g. AMBA with similar
Bombesin peptide analogues specifically bind to
GRPR affinity) because of its biosafety.
Gastrin Releasing Peptide receptors (GRPR) that
are overexpressed on prostate and breast cancers. Materials and Methods:
When radiolabelled diagnostic imaging (e.g. 111In)
In vitro assays using 111In-JMV4168 were
or therapeutic application (e.g. 177Lu) is feasible.
performed on GRPR expressing prostate cancer
Proof of concept has been obtained clinically using PC3 cells. Cell radiation doses were calculated for
peptide agonists, however severe side effects were internalized and cell-surface bound fractions. In
observed in patients. Recent studies have revealed vivo behaviour was tested in PC3 and PC295
the superior profile of GRPR-antagonists as xenografted mice. Biodistribution studies were
compared to agonists. performed 4(-72) h after injection of 10 pmol 111In
(not shown) - or 177Lu-JMV4168, with an extra 4 h
group co-injected with an excess of unlabelled
Results: JMV4168 as specificity control. Also a 1 h dynamic
SPECT/CT imaging study (every 5 min.) with 250
pmol 111In-JMV4168 was performed.
With 111In-JMV4168 73% of the cell dose came
from the cell surface, whereas with 111In-AMBA
82% originated from internalized activity.
Kidneys
Tumours
Discussion and conclusion:
Because of the fast clearance from the GRPR-rich pancreas and background tissues and
high tumour uptake, JMV4168 is a potent bombesin receptor antagonist for safe future
use in clinical imaging and therapy of patients with GRPR-overexpressing tumours.