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 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 non-invasive visualisation of tumour
hypoxia with [18F] HX4 PET imaging in cervix carcinomas; (ii) correlate [18F]
HX4 PET images with blood and tissue markers for hypoxia; (iii) investigate the
quality and optimal timing of [18F] HX4 PET imaging; (iv) compare [18F] HX4 PET
uptake with [18F] FDG PET uptake before treatment and (v) correlate the SUVmax
of [18F] HX4 PET imaging and delta SUVmax with clinical outcome at 3 month
after treatment.

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.