Dj. Honess et al., PRECLINICAL EVALUATION OF THE NOVEL HYPOXIC MARKER TC-99M-HL91 (PROGNOX) IN MURINE AND XENOGRAFT SYSTEMS IN-VIVO, International journal of radiation oncology, biology, physics, 42(4), 1998, pp. 731-735
Citations number
10
Categorie Soggetti
Oncology,"Radiology,Nuclear Medicine & Medical Imaging
Purpose: The Tc-99m-labelled amine oxime Tc-99m-HL91 (Prognox(TM)) is
under investigation as a potential noninvasive clinical marker of tumo
ur hypoxia whose uptake can be monitored by gamma camera imaging. The
aim was to assess its retention in 3 tumours under control and enhance
d oxygenation conditions. Materials and Methods: The SaF murine sarcom
a, grown subcutaneously in CBA mice, and human colon carcinoma HT29 an
d lung adenocarcinoma A549, grown as xenografts in SCID mice, were use
d 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 pO(2) histograph
(KIMOC 6650) with at least 5 tracks and at least 70 values, and expre
ssing pO(2) values as % < 2.5 mmHg, Tc-99m-HL91 (0.8 or 8 MBq per mous
e) was injected i.v. immediately before nicotinamide or saline, and an
imals were killed 2 h after injection. Tumour, skin, muscle, and blood
samples were counted and isotope retention was expressed as % injecte
d dose per gram, C-14-labelled uncomplexed HL91 was used similarly (0.
2-0.4 MBq per mouse) and samples were solubilised and decolourised bef
ore counting. Results: Nicotinamide and carbogen treatment reduced Tc-
99m-HL91 retention in all tumours to 54%-64% of control; it also reduc
ed the proportion of pO(2) values < 2.5 mmHg in all tumours, The mean
proportion of pO(2) values < 2.5 mmHg correlated very well with the me
an ratio of tumour to blood retention at 2 b for all tumours, both unp
erturbed and oxygen-enhanced (r = 0.996; p < 0.001), Retention of C-14
-HL91 in SaF tumour was unchanged by nicotinamide and carbogen, confir
ming that (TC)-T-99m complexation of the ligand is required for hypoxi
a specificity. Conclusion There is excellent correlation between Tc-99
m-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, Tc-99m complexation of the ligan
d is required for hypoxia specificity. Tc-99m-HL91 (Prognox(TM)) shows
good potential as a clinical marker for hypoxia and warrants further
development. (C) 1998 Elsevier Science Inc.