68Ga and 188Re Starch-Based Microparticles as Theranostic Tool for the Hepatocellular Carcinoma: Radiolabeling and Preliminary In Vivo Rat Studies

Elise Verger; Pierre Drion; Geneviève Meffre; Claire Bernard; Luc Duwez; Nicolas Lepareur; Olivier Couturier; François Hindré; Roland Hustinx; Franck Lacoeuille

doi:10.1371/journal.pone.0164626

68Ga and 188Re Starch-Based Microparticles as Theranostic Tool for the Hepatocellular Carcinoma: Radiolabeling and Preliminary In Vivo Rat Studies

PLoS One. 2016 Oct 14;11(10):e0164626. doi: 10.1371/journal.pone.0164626. eCollection 2016.

Authors

Elise Verger^{1

2}, Pierre Drion³, Geneviève Meffre², Claire Bernard², Luc Duwez³, Nicolas Lepareur⁴, Olivier Couturier⁵, François Hindré^{1

6}, Roland Hustinx², Franck Lacoeuille^{1

5

6}

Affiliations

¹ INSERM UMR-S 1066 MINT (Micro- et Nano-médecines Biomimétiques), University of Angers, Angers, France.
² Nuclear Medicine department, CHU de Liège, University of Liège, Liège, Belgium.
³ Animal Facility, Experimental Surgery, GIGA-R & Credec, University of Liège, Liège, Belgium.
⁴ Nuclear Medicine Department, Centre de Lutte Contre le Cancer (CLCC) Eugène Marquis, INSERM U991, Rennes, France.
⁵ Nuclear Medicine department, CHU d'Angers, University of Angers, Angers, France.
⁶ PRIMEX (Plateforme de Radiobiologie et d'IMagerie EXperimentale), University of Angers, Angers, France.

Abstract

Purpose: This work aims to develop, validate and optimize the radiolabeling of Starch-Based Microparticles (SBMP) by 188Re and 68Ga in the form of ready-to-use radiolabeling kits, the ultimate goal being to obtain a unique theranostic vector for the treatment of Hepatocellular Carcinoma.

Methods: Optimal labeling conditions and composition of freeze-dried kits were defined by monitoring the radiochemical purity while varying several parameters. In vitro stability studies were carried out, as well as an in vivo biodistribution as a preliminary approach with the intra-arterial injection of 68Ga radiolabeled SBMP into the hepatic artery of DENA-induced rats followed by PET/CT imaging.

Results: Kits were optimized for 188Re and 68Ga with high and stable radiochemical purity (>95% and >98% respectively). The in vivo preliminary study was successful with more than 95% of activity found in the liver and mostly in the tumorous part.

Conclusion: SBMP are a promising theranostic agent for the Selective Internal Radiation Therapy of Hepatocellular carcinoma.

MeSH terms

Animals
Carcinoma, Hepatocellular / diagnostic imaging*
Gallium Radioisotopes / chemistry
Injections, Intra-Arterial
Isotope Labeling
Liver Neoplasms / diagnostic imaging*
Male
Positron Emission Tomography Computed Tomography
Radiopharmaceuticals / chemistry*
Radiopharmaceuticals / pharmacokinetics
Rats
Rats, Wistar
Rhenium / chemistry*
Starch / chemistry*
Theranostic Nanomedicine
Tissue Distribution

Substances

Gallium Radioisotopes
Radiopharmaceuticals
Rhenium
Starch

Grants and funding

This work has been supported by a grant from the Ministère de l'Enseignement Supérieur et de la Recherche in the frame of the Erasmus Mundus Joint Doctorate NanoFar program (EV); and has been supported in part by a grant from the French National Agency for Research called "Investissements d'Avenir" Labex IRON n°ANR-11-LABX-0018-01 (FH, FL, OC). This work was authorized by Laboratoires Cyclopharma, through patent WO2009013358. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.