Abstract | PURPOSE: MATERIALS AND METHODS: The SaF murine sarcoma, grown subcutaneously in CBA mice, and human colon carcinoma HT29 and lung adenocarcinoma A549, grown as xenografts in SCID mice, were used at 6-8 mm diameter. Oxygenation status was enhanced by giving 500 mg/kg nicotinamide i.p. and breathing carbogen until the point of assay. Oxygenation/ hypoxia was measured using the Eppendorf pO2 histograph (KIMOC 6650) with at least 5 tracks and at least 70 values, and expressing pO2 values as % < 2.5 mmHg. 99mTc-HL91 (0.8 or 8 MBq per mouse) was injected i.v. immediately before nicotinamide or saline, and animals were killed 2 h after injection. Tumour, skin, muscle, and blood samples were counted and isotope retention was expressed as % injected dose per gram. 14C-labelled uncomplexed HL91 was used similarly (0.2-0.4 MBq per mouse) and samples were solubilised and decolourised before counting. RESULTS:
Nicotinamide and carbogen treatment reduced 99mTc-HL91 retention in all tumours to 54%-64% of control; it also reduced the proportion of pO2 values < 2.5 mmHg in all tumours. The mean proportion of pO2 values < 2.5 mmHg correlated very well with the mean ratio of tumour to blood retention at 2 h for all tumours, both unperturbed and oxygen-enhanced (r = 0.996, p < 0.001). Retention of 14C-HL91 in SaF tumour was unchanged by nicotinamide and carbogen, confirming that 99mTc complexation of the ligand is required for hypoxia specificity. CONCLUSION: There is excellent correlation between 99mTc-HL91 retention and hypoxia, as measured by the Eppendorf histograph, over the range of 50%-90% of values < 2.5 mmHg in 3 different tumour models, including 2 human xenografts. 99mTc complexation of the ligand is required for hypoxia specificity. 99mTc-HL91 ( Prognox) shows good potential as a clinical marker for hypoxia and warrants further development.
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Authors | D J Honess, S A Hill, D R Collingridge, B Edwards, G Brauers, N A Powell, D J Chaplin |
Journal | International journal of radiation oncology, biology, physics
(Int J Radiat Oncol Biol Phys)
Vol. 42
Issue 4
Pg. 731-5
(Nov 01 1998)
ISSN: 0360-3016 [Print] United States |
PMID | 9845086
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Contrast Media
- Organotechnetium Compounds
- Oximes
- Radiopharmaceuticals
- technetium Tc 99m 4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime
- Carbon Dioxide
- Niacinamide
- carbogen
- Oxygen
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Topics |
- Adenocarcinoma
(metabolism)
- Animals
- Carbon Dioxide
(administration & dosage)
- Carcinoma
(metabolism)
- Cell Hypoxia
- Colonic Neoplasms
(metabolism)
- Contrast Media
(pharmacokinetics)
- Humans
- Lung Neoplasms
(metabolism)
- Mice
- Mice, Inbred CBA
- Mice, SCID
- Niacinamide
(administration & dosage)
- Organotechnetium Compounds
(pharmacokinetics)
- Oximes
(pharmacokinetics)
- Oxygen
(administration & dosage)
- Radiopharmaceuticals
(pharmacokinetics)
- Sarcoma
(metabolism)
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