title: Targeting human breast tumour in xeno-grafted SCID mice with 99Tcm-glucarate.
abstract: 99Tcm-glucarate accumulation in human mammary BT-20 tumours hosted in severe combined immune deficiency (SCID) mice was compared to 111In-monoclonal antibody 103D2-F(ab')2, 99Tcm-methoxyisobutyl isonitrile (99Tcm-MIBI) and 99Tcm-diethylenetriamine pentaacetate (99Tcm-DTPA). The intracellular tumour distribution of 99Tcm-glucarate was also determined. SCID mice injected with a mixture of 99Tcm-glucarate and 111In-103D2-F(ab')2 were imaged serially up until 24 h. Computer planimetered tumour-to-blood activity (in the heart) ratios (T/BH) to 8 h were significantly greater for 99Tcm-glucarate than 111In-103D2. The mean (+/-S.D.) tumour-to-blood ratio (T/B) from biodistribution was 1.21 +/- 0.31 and 0.35 +/- 0.06 (P < 0.0001) at 5 h, and 1.526 +/- 0.29 and 0.75 +/- 0.2 (P < 0.0001) at 8 h, for 99Tcm-glucarate and 111In-103D2 respectively. At 24 h, T/B for 111In-103D2 (1.76 +/- 0.22) exceeded that of 99Tcm-glucarate (1.44 +/- 0.2, P = 0.01). 99Tcm-glucarate uptake in the tumours at 5 h (1.133 +/- 0.25 %ID g-1) and 8 h (1.213 +/- 0.23 %ID g-1) was significantly greater than that of 99Tcm-MIBI (0.340 +/- 0.09, P = 0.0002; 0.220 +/- 0.04, P = 0.0001) and 99Tcm-DTPA (0.091 +/- 0.03, P < 0.0002; 0.016 +/- 0.01, P < 0.0001) respectively. Intracellular tumour distribution of 99Tcm-glucarate was 50.91 +/- 6.55% in the nuclear fraction, 34.34 +/- 2.88% in the cytoplasmic fraction and 14.75 +/- 7.66% in the mitochondrial fraction. Thus glucarate may provide a 99Tcm-based mammary tumour imaging modality for visualization of tumours very quickly after tracer administration with maximal targeting in the nuclei of the tumour cells.
authors.affiliation: Center for Cardiovascular Targeting, Bouve College of Pharmacy, Northeastern University, Boston, MA, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Petrov
authors.forename: J
authors.initials: J
authors.lastname: Narula
authors.forename: A
authors.initials: A
authors.lastname: Nakazawa
authors.forename: K Y
authors.initials: KY
authors.lastname: Pak
authors.forename: B A
authors.initials: BA
authors.lastname: Khaw
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001943:Breast Neoplasms / Q000000981:diagnostic imaging*; D005260:Female; D015902:Gamma Cameras; D005937:Glucaric Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D008657:Metabolic Clearance Rate; D051379:Mice; D016513:Mice, SCID; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D016719:Radioimmunodetection; D012588:Scintillation Counting; D016284:Technetium Tc 99m Pentetate; D017256:Technetium Tc 99m Sestamibi / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D015609:Organotechnetium Compounds; C067171:technetium Tc 99m glucarate; D017256:Technetium Tc 99m Sestamibi; D005937:Glucaric Acid; D016284:Technetium Tc 99m Pentetate