Phase 1 study to identify tumour hypoxia in patients with head and neck cancer using technetium-99m BRU 59-21.
The aim of this study was to assess the safety and biodistribution of technetium-99m BRU 59-21, a novel radioactively labelled 2-nitro-imidazole hypoxic marker, in head and neck cancer patients and to correlate uptake with pimonidazole staining. (99m)Tc-BRU 59-21 was administered intravenously (mean dose 824 MBq, range 780-857 MBq) to ten head and neck cancer patients scheduled for primary surgery, and whole-body images and SPET scans were then obtained. Uptake of radioactivity in the regions of interest was determined and tumour to normal tissue ratios were calculated after correlative evaluation with MRI/CT. Twelve to 16 h before surgery (up to 2 weeks after the scan), patients received pimonidazole intravenously. Tumour sections were stained immunohistochemically for pimonidazole binding. No serious adverse events were reported. In five patients there were ten adverse events, which were mild in intensity and resolved completely without intervention. Uptake of (99m)Tc-BRU 59-21 was observed in eight of the ten primary tumours. Tumour to normal tissue ratios on the SPET scans for primary tumour and lymph nodes increased from 1.8 (range 0.9-2.7) to 2.1 (range 0.8-3.7) between 30 min and 3 h post injection. Tumour to normal tissue ratios in the primary tumour were significantly correlated with pimonidazole staining for SPET scans performed 30 min and 3 h post injection ( P=0.016 and P=0.037, respectively). When primary tumour and involved lymph nodes were considered in conjunction, correlation between the tumour to normal tissue ratio and pimonidazole staining was observed for early ( P<0.001) but not for late SPET scans ( P=0.076). However, late scans showed better tumour delineation than early scans. Administration of (99m)Tc-BRU 59-21 in head and neck cancer patients appears to be safe and feasible. Uptake and retention in tumour tissue was observed, suggestive of tumour hypoxia, and this was supported by correlations with staining for the hypoxic marker pimonidazole.
Department of Radiotherapy, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
Frank J P
FJ
Hoebers
Hilde L K
HL
Janssen
A Valdés
AV
Olmos
Debbie
D
Sprong
Adrian D
AD
Nunn
Alfons J M
AJ
Balm
Cees A
CA
Hoefnagel
Adrian C
AC
Begg
Karin M G
KM
Haustermans
D015687:Cell Hypoxia; D003131:Combined Modality Therapy; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology / Q000532:radiotherapy; D006801:Humans; D007275:Injections, Intravenous; D007822:Laryngeal Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000532:radiotherapy; D008279:Magnetic Resonance Imaging; D009367:Neoplasm Staging; D009593:Nitroimidazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D016011:Normal Distribution; D015609:Organotechnetium Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000009:adverse effects; D014055:Tomography, Emission-Computed
D009593:Nitroimidazoles; D015609:Organotechnetium Compounds; D011838:Radiation-Sensitizing Agents; D019275:Radiopharmaceuticals; C411943:technetium Tc 99m-BRU-59-21; C033815:pimonidazole