Comparison of [18F]-FMISO, [18F]-FAZA and [18F]-HX4 for PET imaging of hypoxia – a simulation study

Abstract

In line with recent experimental and clinical data, the results suggest that HX4 is a promising new tracer that provides high image contrast four hours p.i., though inter-patient variance can be very high. Nevertheless, the widely used tracer FMISO provides a robust and reproducible signal four hours p.i., but with a lower contrast. The simulations revealed tracer clearance to be the key factor in determining image contrast.

Phase II Study of a Radiotherapy Total Dose Increase in Hypoxic Lesions Identified by 18F-Misonidazole PET/CT in Patients with Non–Small Cell Lung Carcinoma (RTEP5 Study)

“…Lin et al (17) have suggested a low reproducibility of 18 F-FMISO PET images performed within 48 h. More recently, a preclinical study by Busk et al (18) showed a good reproducibility of PET FAZA images acquired within 48 h (r 5 0.82; range, 0.72-0.90), and Zegers et al demonstrated the reproducibility of PET HX4 images in a human study (14). Mathematic simulations based on microscopic tumor tissue sections compared 18 F-FMISO, FAZA, and HX4 and showed that 18 F-FMISO provides a robust and reproducible signal 4 h after injection, with a lower contrast (19). Our observation that 18 F-FMISO-avid tumors have a much worse prognosis confirms that hypoxia imaged on a single PET acquisition is a strong prognostic indicator, making it a relevant target volume for selective radiotherapy dose increase.…”

Correlation of FMISO simulations with pimonidazole‐stained tumor xenografts: A question of O2 consumption?

“…The experimental data were collected in mice using pimonidazole, which show different clearance and diffusion properties that might affect comparability. 26,28 Particularly, pimonidazole shows a faster clearance than clinically used nitroimidazole tracers such as FMISO or FAZA, which was one of the reasons why a simulation time of 4 h was chosen for final comparison. However, the finding that R 2 reaches a stable optimum after approximately 4 h p.i.…”

“…Simulations were performed using a previously described model 18,26 which will be briefly introduced here. Further details are outlined in the Appendix.…”

“…Blood activity was defined by an average blood input function as determined from ten clinical FMISO PET data sets. 26 All simulation steps were implemented in  R2009b. Further simulation details and parameters are outlined in the Appendix (Table III).…”

“…Several approaches have been proposed to simulate oxygen and/or tracer distribution in cancerous tissue. These were performed on vessel maps that are either based on tumor sections [18][19][20] or artificial vessel maps [21][22][23] and results as well as comparisons have been published for several tracers: FMISO, 18,[24][25][26] FAZA, 26 HX4, 26 and CuATSM (Refs. 22 and 24).…”