Non invasive imaging of [18F]HX4 with Positron-Emission-Tomography (PET) in Cervix Cancer.

Tumor hypoxia is the situation where tumor cells are or have been deprived of
oxygen. Hypoxic tumor cells are usually more resistant to radiotherapy and
chemotherapy and more likely to develop metastasis. In Cervix cancer, tumor
hypoxia is known to be an important prognostic factor for long term survival.
[18F]HX4 is being developed as a diagnostic radiopharmaceutical for PET imaging
to find a marker for hypoxia that can be used in standard clinical practice.
Current hypoxia tracers lack reliable image quality and kinetics. Because of
the short half life and clearance, we expect that [18F]HX4 will have a higher
tumor to background ratio than current nitro-imidazole hypoxia markers such as
[18F]-misonidazole. In a recent phase 1 clinical study from van Loon et al1,
PET-imaging with [18F]HX4 was feasible without any toxicity. The clinical use
of a reliable, non-invasive and easy to use hypoxia imaging agent could allow
selection of patients most likely to benefit from hypoxia modifying therapies.

The aim of this study is to (i) determine if tumor hypoxia can be accurately
visualized with [18F] HX4 PET imaging in Cervix tumors (ii) correlate the [18F]
HX4 PET images with blood and tissue markers and (iii) investigate the quality
and optimal timing of [18F] HX4 PET imaging (iv) compare [18F] HX4 PET uptake
with [18F] FDG PET uptake before and after treatment and (v) analyse
correlation with responses

A non-randomized, open label trial.
Eligible patients with squamous cell carcinoma, adenocarcinoma or adenosquamous
carcinoma (FIGO stage IB - IVA), to be treated with curative radiation
treatment either or not combined with concurrent chemotherapy or deep
hyperthermia are included.

4.1 Before treatment
A standard clinical [18F]FDG PET-CT will be performed for the radiotherapy
planning.
After a minimum time interval of 24 hours, baseline [18F]HX4 PET scans will be
performed:
Based on the phase I trial1 444 MBq (12 mCi) [18F]HX4 is administrated via a
bolus IV injection.
The first image acquisition is started together with the administration of
[18F]HX4 (30-40 min dynamic). Static scans are acquired at 90 min, 180 min and
240 min p.i.*
4.2 Treatment
Radiation treatment (either or not combined with chemotherapy or hyperthermia)
will be performed according to the institutional protocol.

During treatment
[18F]HX4 scans (dynamic, 90, 180 and 240 min p.i.*) will be repeated after
radiotherapy treatment with 20 ± 4 Gy (approximately two weeks), by
administrating 444MBq (12mCi) [18F]HX4 via a bolus IV injection.

4.3 Follow up:
according to the institutional protocol.

all patients will be monitored closely during and after administration of the
labeled [18F]HX4 .The proposed dosis [18F]HX4 is chosen based on the results
of the phase I trial with [18F]HX4. In view of previous experiences wtih
[18F]HX4, conventional FDG-PET CT an other nitroimidazole drugs, we expect no
unforseen side effects.