Tumor uptake of copper-diacetyl-bis(N(4)-methylthiosemicarbazone): effect of changes in tissue oxygenation.

UNLABELLED: We showed previously that, in vitro, copper-diacetyl-bis(N(4)-methylthiosemicarbazone) (Cu-ATSM) uptake is dependent on the oxygen concentration (pO2). We also showed that, in vivo, Cu-ATSM uptake is heterogeneous in animal tumors known to contain hypoxic fractions. This study was undertaken to confirm the pO2 dependence of this selective uptake in vivo by correlating Cu-ATSM uptake with measured tumor pO2. METHODS: Experiments were performed with the 9L gliosarcoma rat model using a needle oxygen electrode to measure tissue pO2. Using PET and electronic autoradiography, Cu-ATSM uptake was measured in tumor tissue under various pO2 levels. The oxygen concentration within implanted tumors was manipulated by chemical means or by altering the inhaled oxygen content. RESULTS: A good correlation between low pO2 and high Cu-ATSM accumulation was observed. Hydralazine administration in animals caused a decrease in the average tumor pO2 from 28.61 +/- 8.74 mm Hg to 20.81 +/- 7.54 mm Hg in untreated control animals breathing atmospheric oxygen. It also caused the tumor uptake of Cu-ATSM to increase by 35%. Conversely, in animals breathing 100% oxygen, the average tumor pO2 increased to 45.88 +/-15.9 mm Hg, and the tumor uptake of Cu-ATSM decreased to 48% of that of the control animals. PET of animals treated in a similar fashion yielded time-activity curves showing significantly higher retention of the tracer in hypoxic tissues than in oxygenated tissues. CONCLUSION: These data confirm that Cu-ATSM uptake in tissues in vivo is dependent on the tissue pO2, and that significantly greater uptake and retention occur in hypoxic tumor tissue. Therefore, the possible use of Cu-ATSM PET as a prognostic indicator in the management of cancer is further validated.

Computed radiography versus screen-film radiography: detection of pulmonary edema in a rabbit model that simulates neonatal pulmonary infiltrates.

PURPOSE: To determine if computed radiography is equivalent to screen-film radiography in depicting pulmonary edema and to determine if radiation exposure can be reduced with computed radiography while maintaining equivalent diagnostic accuracy for pulmonary edema. MATERIALS AND METHODS: Oleic acid was intravenously injected into three rabbits at each of four doses: 0, 0.02, 0.04, and 0.06 mL/kg. Two hours later, chest computed radiographs and screen-film radiographs were obtained at 60 kVp and 1.1 mAs. Additional computed radiographs were obtained after reducing milliampere seconds or by reducing milliampere seconds and increasing the kilovolt peak, which reduced bone marrow exposure by up to 20%. The presence of pulmonary opacities, "truth," was established by the wet-dry weight ratio and by chest computed tomography (CT). The radiographs were masked and randomized. Four observers rated the images for the presence of parenchymal opacities with a dichotomous score and judged the quality of the radiographs on a scale from 1 (worst) to 6 (best). Cochran Q tests and McNemar tests were used to analyze the differences in paired comparisons. Image quality was evaluated with logistic regression analysis. RESULTS: There was no significant difference between truth and observer ability to detect opacity for either modality or for any exposure (P > .05). There was no significant difference between computed radiography and screen-film radiography for image quality (P > .05). CONCLUSION: Computed radiography is equivalent to screen-film radiography in the detection of pulmonary edema. Radiation exposure reduction of 20% can be achieved without affecting pulmonary edema detection or image quality.

Evaluation of two new gadolinium chelates as contrast agents for MRI.

Two new gadolinium chelates were investigated for potential use as tissue-specific contrast agents for magnetic resonance imaging. In vitro measurements of stability constants, octanol/water partition coefficients and relaxation times in solutions of water and human serum albumin (HSA) were performed with each new chelate and compared with gadolinium-diethylenetriamine pentaacetic acid, Gd(DTPA). Biodistribution studies and magnetic resonance imaging in rats were used to evaluate the new chelates in vivo. The stability constants (log K) of gadolinium-N,N''-bis(3-hydroxy-6-methyl-2- pyridylmethyl)diethylenetriamine-N,N',N''-triacetic acid, Gd(DTTA-HP), and gadolinium-1,7,13-triaza-4,10,16-trioxacyclooctadecane-N,N', N''-triacetic acid, Gd(TTCT), were determined to be 23.65 and 18.07, respectively. These can be compared to a literature value of 22.46 for Gd(DTPA). Octanol/water partition coefficients for both complexes showed they were more lipophilic than Gd(DTPA). Gd(DTTA-HP) exhibited a smaller relaxivity in water but a larger relaxivity in 4% HSA than Gd(DTPA). Gd(TTCT) exhibited a lower relaxivity than Gd(DTPA) in both water and 4% HSA. Both complexes showed similar biodistributions to Gd(DTPA) no carrier-added concentrations. Gd(DTTA-HP) had a greater percent change in signal intensity than Gd(DTPA) on T1-weighted spin-echo images in the heart, liver, and kidney. Percent change in signal intensity for Gd(TTCT) was lower than Gd(DTPA) in heart, liver, and kidney.