Comparison and evaluation of two RGD peptides labelled with 68Ga or 18F for PET imaging of angiogenesis in animal models of human glioblastoma or lung carcinoma
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Claire Provost1,2, Aurélie Prignon1, Laura Rozenblum-Beddok1,3, Quentin Bruyer2, Sylvie Dumont4, Fatiha Merabtene4, Valérie Nataf3, Cédric Bouteiller2 and Jean-Noël Talbot1,3
1Laboratoire d'Imagerie Moléculaire Positonique (LIMP), UMS 28, Sorbonne Université, Paris, France
2PETNET Solutions SAS, Siemens Healthineers, Lisses, France
3Service de Médecine Nucléaire et Radiopharmacie, Hôpital Tenon, AP-HP Paris, France
4Plateforme d'Histomorphologie Service d'Anatomie Pathologique, Hôpital Saint Antoine, AP-HP, Paris, France
Claire Provost, email: [email protected]
Keywords: preclinical PET; integrins αvβ3; angiogenesis; 68Ga-RGD; 18F-RGD-K5
Received: October 15, 2017 Accepted: March 19, 2018 Published: April 10, 2018
The aim of this study was to evaluate two RGD radiotracers radiolabelled with fluorine-18 or gallium-68, in detecting angiogenesis in grafted human tumours and monitoring their treatment with the anti-angiogenic agent bevacizumab.
Sixteen mice bearing an U87MG tumour in one flank and a contralateral A549 tumour were treated with intravenous injections of bevacizumab twice a week for 3 weeks. PET images with 18F-RGD-K5 and 68Ga-RGD were acquired before treatment (baseline), after three bevacizumab injections (t1) and after seven bevacizumab injections (t2).
In A549 tumours, the treatment stopped the tumour growth, with a tumour volume measured by calliper remaining between 0.28 and 0.40 cm3. The decrease in tumour uptake of both RGD tracers was non-significant. Therefore it was not possible to predict this efficacy on tumour growth based on RGD PET results, whereas ex vivo measurements showed a significantly lower tumour uptake of both tracers in mice sacrificed at t2 vs. at baseline.
In U87MG tumours, the uptake measured on PET decreased during treatment, reflecting the partial therapeutic effect observed on tumour volume, consisting in a decrease in the slope of tumour growth. Using 18F-RGD-K5, this decrease in tumour SUVmax became significant at t1, whereas it was also observed with the 68Ga-RGD tracer, but only at t2. 18F-RGD-K5 appeared more efficient than 68Ga-RGD in the visualisation and follow-up of U87MG tumours.
The comparison of those results with those of immunohistochemistry at baseline and at t2 favoured the hypothesis that tumour RGD uptake reflects other cancer properties than just its angiogenic capacity.
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