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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antineoplastic effect of heavy water on the growth of xenotransplanted human carcinoma was compared to that of 2 cytostatic drugs. Seven-week-old BALB/c-nu/nu mice were inoculated subcutaneously with a poorly differentiated oropharyngeal squamous-cell carcinoma, or with variants of carcinoma of the large intestine. After tumor inoculation, 3 subgroups of mice were treated by: (i) moderately deuterated drinking water; (ii) i.p. injections of 5-Fluoro-uracil (5-FU) or Bleomycin; (iii) a combination of deuterated drinking water and of the cytostatic drugs. Control mice were not treated. Heavy water delayed growth of all carcinoma variants. The cytostatic drugs slowed down the growth of the 2 poorly differentiated tumor variants. Conversely, 5-FU did not retard the growth of the moderately well differentiated colon carcinoma. Heavy water combined with either cytostatic drug showed synergistic effects in the 2 poorly differentiated tumor variants. The tumors of treated animals weighed 36% to 90% less than those of control animals. The antineoplastic effects were more conspicuous in poorly than in moderately well differentiated tumor variants. Cytokinetic parameters such as labelling indices following application of 5-125I-Iodo-2'deoxyuridine, and of Ki-67, a monoclonal antibody (MAb) directed against an antigen of proliferating cells, or mitotic indices and tumor volume doubling time, combined with the results of histologic evaluation of the tumors, suggested an underlying deuterium-induced prolongation of tumor-cell cycle times and a reduction of the growth fraction.
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PMID:Heavy water enhances the antineoplastic effect of 5-fluoro-uracil and bleomycin in nude mice bearing human carcinoma. 168 3

Fluoromisonidazole (FMISO) has been shown to bind selectively to hypoxic cells in vitro and in vivo at radiobiologically significant oxygen levels. When labeled with the positron emitter fluorine-18 (F-18), its uptake in tissue can be detected quantitatively with high precision by positron emission transaxial tomography (PETT). This paper presents the first experiences with PETT imaging of [F-18]FMISO uptake in human malignancies, and describes the development of this technique as a tool for the non-invasive assessment of tumor hypoxia. Eight patients with selected cancers were imaged prior to primary radiotherapy, and 3 returned for follow-up scans, for a total of 11 imaging studies. Six of eight pre-radiotherapy studies revealed retention of [F-18]FMISO in tumors that significantly exceeded plasma concentrations by 2 hr after drug injection; all five patients with head and neck primaries had such "positive" scans. An analytic method for the interpretation of [F-18] FMISO PETT images is presented, defining hypoxic elements within a tumor volume as regions with a threshold regional tumor:plasma [F-18]FMISO ratio of greater than or equal to 1.4 by 2 or more hours after injection. Toward the end of a course of fractionated radiotherapy, three repeat studies in patients with initially positive scans showed no tumor accumulation of drug above the threshold ratio of 1.4, suggesting reoxygenation had occurred. Pharmacokinetic and dosimetry data support continued use of [F-18]FMISO as a safe hypoxia probe. Two imaging protocols have been developed for human studies; a long protocol allows for more complete biodistribution and dosimetry information, and a shorter protocol facilitates increased patient accrual by applying a simple, clinically expedient imaging procedure. When correlated with tumor outcome, [F-18]FMISO PETT imaging may be developed as a predictor of tumor response to conventional radiotherapy. The implications of this technique in addressing persistent questions of tumor hypoxia in human oncology is discussed.
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PMID:Imaging of hypoxia in human tumors with [F-18]fluoromisonidazole. 172 19

Positron emission tomography (PET) with fluorine-18 fluoro-2-deoxy-D-glucose (FDG) was performed in 19 patients referred for clinical evaluation of soft-tissue masses. These patients had 20 different lesions and had been evaluated previously with computed tomography (CT) and/or magnetic resonance (MR) imaging. The diagnoses were subsequently confirmed with open biopsy or excision (19 lesions) or by clinical and radiographic follow-up (one lesion). Semiquantitative assessment of FDG accumulation (differential uptake ratio) within the suspected tumor helped correctly separate the 10 malignant tumors from the 10 benign lesions. In contrast, a simple ratio of FDG uptake within the suspected tumor to that within comparable normal soft tissue was less successful in helping make this distinction, with overlap in 12 of the 20 cases. Careful comparison with findings from other available imaging studies is essential for accurate interpretation of PET studies of soft-tissue masses, but in many cases, PET may be a useful adjunct in the preoperative evaluation of suspected soft-tissue tumors, yielding valuable information that is not provided with CT or MR imaging.
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PMID:PET evaluation of soft-tissue masses with fluorine-18 fluoro-2-deoxy-D-glucose. 172 80

Seventeen pediatric patients with posterior fossa brain tumors were studied with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) and positron emission tomography (PET). The FDG uptake was ranked by two observers, and the results were correlated with tumor histology. Increased FDG uptake was associated with more malignant and aggressive tumor types. Heterogeneity of FDG uptake was associated with previous therapy, including radiation therapy and chemotherapy. 2-[18F]Fluoro-2-deoxy-D-glucose PET will likely be an important adjunct in the management of pediatric posterior fossa tumors, much as in adult patients with brain tumors.
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PMID:FDG-PET in pediatric posterior fossa brain tumors. 172 8

The value of positron emission tomography (PET) and magnetic resonance (MR) imaging in differentiating recurrent rectal cancer and scar was investigated. PET with fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) and MR imaging were performed in 15 patients with suspected recurrence. FDG accumulation in the mass was measured by means of the differential absorption ratio (DAR). All 11 patients with confirmed recurrent rectal cancer had increased accumulation of FDG in the mass (DAR = 4.73 +/- 2.28). Low FDG accumulation in the mass (DAR = 0.97 +/- 0.15) was noted in the remaining four patients, in whom the presence of a scar was proved by means of follow-up observation with or without biopsy. On the MR images, the recurrent tumor could be differentiated from scar in all but one case. The lesion-muscle signal intensity ratios on the T2-weighted images for the recurrent tumor and scar were 2.18 +/- 0.55 and 0.89 +/- 0.30, respectively. PET and MR imaging complement each other in the differential diagnosis between recurrent rectal cancer and scar. PET may also permit the evaluation of the effect of therapy.
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PMID:Recurrent rectal cancer and scar: differentiation with PET and MR imaging. 173 79

Pharmacokinetic characterization of various nitroazole radiosensitizers was carried out to clarify the effect of fluorine modification of the side-chain groups on the sensitizing activity and the acute toxicity. The in vivo tumor/plasma partition coefficient (PTP) of sensitizers increased with increase in the octanol/water partition coefficient (Pow) up to approximately 0.3 and was almost unity (maximum) for sensitizers with their Pow values larger than approximately 0.3. This relationship was observed commonly for all types of sensitizers independent of the fluorine modification. The in vivo brain/plasma partition coefficient (PBP) of sensitizers increased with increase in the Pow, attaining a constant value of almost unity at Pow greater than 0.5 for non-fluorine sensitizers or at Pow greater than 1.5 for fluorine-modified sensitizers. The maximum brain-affinity factor ((FB,t)max = (CB,t)max/Ds, where (CB,t)max and Ds are the maximum intrabrain concentration and the administered dose of sensitizer, respectively) was proportional to the maximum tumor-affinity factor ((FT,t)max = (CT,t)max/Ds, where (CT,t)max is the maximum intratumor concentration of sensitizer), depending on the side-chain structure of the sensitizer. A series of non-fluorine and fluorine-modified nitroazole derivatives, including N-(2'-hydroxyethyl)-2,2-difluoro-3-(3''-nitro-1'-triazolyl)propionamide (KU-2285), gave a smaller brain to tumor ratio of approximately 1/7. The toxicity index defined by 1/LD50/7 was parallel to the sensitizing activity measured by 1/DS,1.5 (DS,1.5 is the sensitizer dose to obtain the SER of 1.5 in vivo). The therapeutic risk index defined by Ds,1.5/LD50/7 depended on the side-chain structures of sensitizers. The DB,1-5LD50-/7 values of KU-2285 and ethanidazole (SR-2508) were 1/3 that of misonidazole (MISO). The sensitizers were smaller Ds,1.5/LD50/7 values showed higher sensitizing activities as their tumor affinities increased, without an increase in serious toxicity.
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PMID:Fluorine modification of nitroazole radiosensitizers for the enhancement of sensitizing activity with lowering toxicity: a pharmacokinetic characterization. 173 99

A mixture of perfluoromethyldecahydroisoquinoline (FMIQ) emulsion coupled with anti-CEA (carcinoembryonic antigen) antibody and perfluorotripropylamine (FTPA) was injected into a nude mouse inoculated with human colon carcinoma LS174T. Three days after the injection, in vivo fluorine-19 chemical shift images of the spectral signals of the two perfluorocarbons (PFCs) were obtained simultaneously. The signal intensities and distributions of FMIQ and FTPA were similar in the liver and spleen but different in the tumor. FMIQ was detected in almost the entire tumor, with scattered areas of high uptake. FTPA, however, was detected only in the center of the tumor. The results suggest that F-19 chemical shift imaging of two PFCs, one coupled to antibody and the other not, has potential application in tumor diagnosis.
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PMID:In vivo F-19 chemical shift imaging with FTPA and antibody-coupled FMIQ. 182 76

To develop new hypoxic cell radiosensitizers, we incorporated fluorine atoms into the side chain of the 2-nitroimidazole. Of the resulting compounds, KU-2285 (a 2-nitroimidazole with an N1-substituent of CH2CF2CONHCH2-CH2OH) was considered the most useful as a hypoxic cell radiosensitizer. In this study, its in vivo radiosensitizing activity and acute toxicity were compared with those of etanidazole. The reduction potentials of KU-2285 and etanidazole were -0.96 V and -1.05 V vs Ag/Ag+ in N,N-dimethylformamide, respectively, and their respective octanol/water partition coefficients were 0.25 and 0.040. The in vivo radiosensitizing activity of KU-2285 was found to be similar to that of etanidazole at the same administration dose when assayed by an in vivo-in vitro assay, a growth delay assay, and a tumor control assay using SCC VII tumor or transplanted mammary tumor in C3H/He mice. Although the radiosensitizing activity of etanidazole was reduced when it was administered orally, there was no significant difference in the radiosensitizing activity of KU-2285 whether it was administered intravenously, intraperitoneally, or orally. The acute toxicity measured as the LD50/7 in 8-week-old female C3H/HeJ mice was found to be 2.4 g/kg (intravenously), 2.1 g/kg (intraperitonealy), and 4.25 g/kg (orally) for KU-2285, whereas it was 4.75 g/kg (intravenously) for etanidazole.
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PMID:A fluorinated 2-nitroimidazole, KU-2285, as a new hypoxic cell radiosensitizer. 182 62

The influence of infusion time and dose on the anticancer efficacy of 5-fluoro-2'-deoxyuridine (FdUrd) was investigated using a locoregional therapy model: Novikoff hepatoma transplanted i.m. into the thigh of Wistar rats and FdUrd infusion via a catheter implanted in the femoral artery. In experiment A the FdUrd dose (five daily doses of 12, 19 and 30 mg/kg) and the duration of administration (bolus, 1 h, 5 h, and 24 h) were varied. The change in tumor volume following treatment and the number of rats showing regression vs progression served as indicators of therapy response. The results showed a clear dose dependence, and for each infusion time the 30 mg/kg dose was the most effective, without any signs of general toxicity. At this dose the longest infusion time (24 h) was less effective (regression in three of six rats) compared with 1-h or 5-h treatments (four of five in regression). In experiment B either one or five daily FdUrd doses (15, 30, 60 mg/kg) were administered i.a. for the same infusion times used in experiment A. After treatment, tumors were explanted ex vivo and approximately 1-g tissues samples were immediately frozen in liquid nitrogen for storage. 19F-NMR spectroscopy at 11.7 T was used to quantify FdUrd metabolites [5-fluorouracil (FUra), alpha-fluoro-beta-alanine (F beta Ala), 5-fluorouracil nucleosides and nucleotides (F-Nuc)] in the solid tumor tissue samples (maintained at 4 degrees C) with a detection threshold of about 5 nmol/g. The metabolite signal pattern indicated that FdUrd is first converted to FUra, followed by anabolism primarily to nucleotides in the oxy form (e.g. FUTP). The total amount of fluorine detected in tumor tissue increased with dose and decreased with infusion time. For all treatments FNuc could be detected, even after 24 h infusion, and their levels showed a good linear correlation with the total F. The major catabolite F beta Ala was present in tumor at low levels that correlated poorly with total F, indicating recirculation from other organs (e.g. liver) as the main source. Thus, the NMR method can provide detailed information regarding the efficiency of locoregional treatment (catheter function, drug uptake and metabolism). Initial results of non-invasive in vivo NMR experiments are also presented.
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PMID:Locoregional administration of 5-fluoro-2'-deoxyuridine (FdUrd) in Novikoff hepatoma in the rat: effects of dose and infusion time on tumor growth and on FdUrd metabolite levels in tumor tissue as determined by 19F-NMR spectroscopy. 182 30

In a rat AH109A tumor model, metabolic tracers for glucose, amino acid, and nucleic acid metabolisms (2-deoxy-2-[18F]fluoro-D-glucose (18FDG), L-[methyl-14C]methionine (14C-Met), [6-3H]thymidine (3H-Thd), and 2'-deoxy-5-[18F]fluorouridine (18FdUrd], and the conventional radionuclide 67Ga-citrate were used to assess the feasibility of monitoring tumor radiotherapy using a quadruple tracer technique. Two combinations of four tracers (18FDG or 18FdUrd, 14C-Met, 3H-Thd and 67Ga) were compared in a time-course study after single-dose irradiation (20 Gy) and were also used in a dose-dependency study performed 6 days after 5, 10, 15, or 20 Gy of irradiation. Fluorine-18-FDG showed a large change in uptake and a steady response to radiotherapy. Fluorodeoxyuridine showed a rapid decrease after radiotherapy, but the range of change in uptake was narrow. Gallium-67 could not detect tumor response early after treatment, but showed a marked change in uptake later. [6-3H]Thd and 14C-Met showed a rapid response to irradiation and a high sensitivity for monitoring radiotherapy, suggesting that they may be feasible for PET studies.
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PMID:Tracer feasibility for monitoring tumor radiotherapy: a quadruple tracer study with fluorine-18-fluorodeoxyglucose or fluorine-18-fluorodeoxyuridine, L-[methyl-14C]methionine, [6-3H]thymidine, and gallium-67. 194 Nov 48


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