(18)F]VM4-037 MicroPET Imaging and Biodistribution of Two In Vivo CAIX-Expressing Tumor Models.

Sarah G J A Peeters,Dennis Laan,Martien Mooijer,Albert D Windhorst,Claudiu T Supuran,Philippe Lambin,Robert C Schuit,Daniela Vullo,Natasja G Lieuwes,Jonas Eriksson,Ludwig Dubois

doi:10.1007/s11307-015-0831-y

Abstract

Purpose[18F]VM4-037 was recently developed as a positron emission tomography (PET) tracer for the detection of carbonic anhydrase IX (CAIX), a tumor-specific protein upregulated under hypoxic conditions. In this study, the accumulation of [18F]VM4-037 was determined in two CAIX-expressing preclinical human tumor models.ProceduresU373 and HT29 tumor-bearing animals were injected with [18F]VM4-037 and underwent microPET imaging up to 4 h post-injection (p.i.). Biodistribution throughout the different organs was assessed at 2 and 4 h p.i. using gamma counting.ResultsMicroPET imaging showed high [18F]VM4-037 uptake in the abdominal region, and biodistribution revealed high radioactivity in the kidney, ileum, colon, liver, stomach, and bladder. Although high CAIX expression was confirmed in both tumor models, tumor uptake assessed with microPET and biodistribution experiments was comparable to background tissues.ConclusionsIn this study, [18F]VM4-037 does not specifically accumulate in CAIX-expressing tumors, indicating that the tracer is not suitable for the detection of CAIX.

Highlights

Carbonic anhydrase IX (CAIX) is a tumor-specific protein upregulated in response to hypoxia [1]
Purpose: [18F]VM4-037 was recently developed as a positron emission tomography (PET) tracer for the detection of carbonic anhydrase IX (CAIX), a tumor-specific protein upregulated under hypoxic conditions
High CAIX expression was confirmed in both tumor models, tumor uptake assessed with microPET and biodistribution experiments was comparable to background tissues

Summary

Introduction

Carbonic anhydrase IX (CAIX) is a tumor-specific protein upregulated in response to hypoxia [1]. Recent publications show that inhibition of CAIX results in reduced tumor growth in vivo, especially in combination with radiotherapy [7, 8]. S.G.J.A. Peeters et al.: [18F]VM4-037 tumor imaging in vitro and in vivo results indicate the potential involvement of CAIX in processes like metastasis and invasion [9,10,11]. Before clinical implementation of these specific inhibitors, it would be extremely valuable to have a screening method to assess the CAIX status of tumors. This would allow patient selection before the start of treatment. A new promising imaging radiopharmaceutical, [18F]VM4-037, has recently been proposed. We assessed the tumor-specific uptake of this positron emission tomography (PET) radiopharmaceutical in two preclinical CAIX-expressing tumor models using microPET and biodistribution

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