Tumor blood ratio

Thus far, the EPR effect has been credited for the clinical development of SMANCS and the pHPMA-doxombicin conjugate (PKl) For example, arterially administered SMANCS in patients with primary hepatoma displayed tumor/blood ratios as great as 2000 when combined with Lipidol as carrier Furthermore, the clinical trials ofPKl suggested that this dmg displayed antitumour activity in chemotherapy-refractory patients, considerably reduced toxicity compared with doxombicin, and provided evidence of tumor-selective targeting... 

A number of carboranyl porphyrins have been obtained on the basis of the natural porphyrin derivatives, such as deuteroporphyrin IX and hematoporphyrin IX, and two of than, VCDP and BOPP (Figure 9.12), have been extensively studied in animals. BOPP was reported to have a tumor-normal brain ratio from 13 1 to 400 1 for different glioma models [117,118]. High boron levels in tumor (>60 pg °B/g tumor) were achieved in these animal studies. However, data obtained from a human Phase I clinical trial showed that under intravenous injection BOPP does not deliver therapeutic concentrations of boron to the tumors of glioblastoma patients, and dose escalation is prevented by the toxicity of this compound. Nevertheless, BOPP has shown some promise as an effective PDT photosensitizer [119-121]. More recently, it was demonstrated that convection-enhanced delivery of BOPP significantly enhances the boron concentration in tumors and produces very favorable tumor-brain and tumor-blood ratios [122]. 

Many methods for measurement of tumor blood flow are based on quantifying the tumor uptake of a systemically administered tracer. Such uptake will obviously be a function of regional blood flow, but it will also depend on the arterial input function and the efficiency with which the tracer is extracted from the blood during passage through the microvasculature. The latter parameter is defined as the extraction ratio (ER) ... 

Compound Time (Hrs) Tumor Blood Muscle (Tumor/Tissue Ratios in Liver Kidney Parentheses) TCI... 

However, the concentration of the radiolabel in the blood remains higher than in the target organs, giving poor uterus/muscle and mammary gland/blood ratios. Despite this disadvantage, an MCF-7 tumor implanted in 8-week-old female athymic NCr-nu/nu mice was visible by SPECT camera. 

The successful application of boron neutron capture therapy (BNCT) is dependent on the identification and preparation of boron-containing compounds that can be delivered to and retained by the tumor in significant amounts (>15 pg boron/g tumor) (Fairchild and Bond, 1985). Compounds targeted for application in BNCT must either accumulate in the tumor through natural mechanisms or, in the case of compounds that have no natural propensity for the tumor, be delivered to the tumor using a tumor-specific delivery modality. In addition to the required tumor boron concentration, the selected compounds should yield in vivo biodistributions with tumor to normal tissue (including blood) ratios of three or higher and be sufficiently nontoxic (Hawthorne, 1993 Soloway et al., 1998). 

The median and left lateral lobes of the livers of three 150-g. rats were removed, and labeled phosphate was injected by way of the femoral vein 36 hours later. Normal rats and rats bearing bilateral carcinoma 256 implants were injected at the same time. Two days later the livers were cleared of blood by perfusion with saline, and the nuclei were isolated from the livers and tumors. For the normal liver the ratio of activity per milliter of nuclei to activity per gram of tissue was 0.345, while for regenerating liver and tumor the ratios were 1.02 and 1.08, respectively. 

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