In Vivo Monitoring of the Antiangiogenic Effect of Neurotensin Receptor-Mediated Radiotherapy by Small-Animal Positron Emission Tomography: A Pilot Study

Pharmaceuticals

Simone Maschauer¹  Tina Ruckdeschel¹  Philipp Tripal¹  Roland Haubner³  Jürgen Einsiedel²  Harald H࿋ner²  Peter Gmeiner²  Torsten Kuwert¹ 

[1] Department of Nuclear Medicine, Laboratory of Molecular Imaging and Radiochemistry, Friedrich Alexander University, Schwabachanlage 6, 91054 Erlangen, Germany; E-Mails:;Department of Chemistry and Pharmacy, Medicinal Chemistry, Emil Fischer Center, Friedrich Alexander University, Schuhstraße 19, 91052 Erlangen, Germany; E-Mails:;Department of Nuclear Medicine, Innsbruck Medical University, Anichstr. 35, 6020 Innsbruck, Austria; E-Mail:

关键词: neurotensin receptor;    positron emission tomography;    radiotherapy;    lutetium-177;    RGD peptide;    angiogenesis;   

DOI  :  10.3390/ph7040464

来源: mdpi

【 摘 要 】

The neurotensin receptor (NTS1) has emerged as an interesting target for molecular imaging and radiotherapy of NTS-positive tumors due to the overexpression in a range of tumors. The aim of this study was to develop a ¹⁷⁷Lu-labeled NTS1 radioligand, its application for radiotherapy in a preclinical model and the imaging of therapy success by small-animal positron emission tomography (µPET) using [⁶⁸Ga]DOTA-RGD as a specific tracer for imaging angiogenesis. The ¹⁷⁷Lu-labeled peptide was subjected to studies on HT29-tumor-bearing nude mice in vivo, defining four groups of animals (single dose, two fractionated doses, four fractionated doses and sham-treated animals). Body weight and tumor diameters were determined three times per week. Up to day 28 after treatment, µPET studies were performed with [⁶⁸Ga]DOTA-RGD. At days 7–10 after treatment with four fractionated doses of 11–14 MBq (each at days 0, 3, 6 and 10), the tumor growth was slightly decreased in comparison with untreated animals. Using a single high dose of 51 MBq, a significantly decreased tumor diameter of about 50% was observed with the beginning of treatment. Our preliminary PET imaging data suggested decreased tumor uptake values of [⁶⁸Ga]DOTA-RGD in treated animals compared to controls at day 7 after treatment. This pilot study suggests that early PET imaging with [⁶⁸Ga]DOTA-RGD in radiotherapy studies to monitor integrin expression could be a promising tool to predict therapy success in vivo. Further successive PET experiments are needed to confirm the significance and predictive value of RGD-PET for NTS-mediated radiotherapy.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.