Tumor cell spheroids as a model for evaluation of metabolic changes after irradiation.

UNLABELLED: Tumor cell spheroids provide a good model to evaluate the relationship between tumor volume and the number of viable cells in the volume with the uptake of metabolic tracers before and after therapy. They represent the only in vitro model that allows the determination of the activity per unit volume, a parameter which is relevant for interpretation of PET studies. The purpose of this study was to evaluate this model with respect to the uptake of 14C-FDG, 3H-methionine and 3H-thymidine with and without exposure to irradiation. METHODS: Spheroids of the human adenocarcinoma cell line SW 707 were incubated in media containing 14C-FDG, 3H-methionine or 3H-thymidine for 1 hr at 1, 4, 8, 24 and 48 hr after exposure to a single radiation dose of 6 Gy together with control spheroids. Tracer uptake after incubation was expressed in cpm/ spheroid, cpm/1000 viable cells and cpm/0.01 mm3. In addition, the proliferative capacity of control and irradiated spheroids was determined using the clonogenic assay. RESULTS: Spheroid uptake of FDG decreased with time after irradiation, while the uptake per 1000 viable cells was increased significantly. The activity per unit volume remained unchanged in comparison to control spheroids. Methionine uptake per spheroid was unchanged after irradiation because of the high increase in uptake per 1000 viable cells. Uptake per unit volume also remained unchanged in comparison to controls. Thymidine uptake per 1000 viable cells did not change after irradiation but showed significant differences in uptake per spheroid and per unit volume compared to controls. The percentage of thymidine incorporated into the TCA-precipitable fraction containing DNA was 50% in controls and decreased to 12% at 24 hr after irradiation. The suppressed clonogenic capacity early after therapy recovered with the increase in thymidine uptake and with the increase in thymidine incorporation into DNA. CONCLUSION: The results show that the activity determined within a certain tumor volume is a balance between the increased tracer uptake by surviving cells after therapy and the lack of tracer uptake by dead cells, which still contribute to the tumor volume. Thus, the resulting unchanged activity per unit volume within the spheroid, as found for FDG and methionine, may not fully reflect therapy-induced metabolic changes in tumors.

[Effect of occupational lead exposure on various elements in the human blood. Effects on calcium, cadmium, iron, copper, magnesium, manganese and zinc levels in the human blood, erythrocytes and plasma in vivo]. / Die Beeinflussung verschiedener Elemente im menschlichen Blut durch berufliche Bleiexposition. Zur in vivo Beeinflussung der Calcium-, Cadmium-, Eisen-, Kupfer-, Magnesium-, Mangan- und Zinkkonzentrationen im menschlichen Vollblut, Erythrozyten und Plasma.

The influence of occupational lead-exposure on calcium, magnesium and trace elements concentration in blood was investigated. We examined 96 lead-exposed persons and for comparison 46 persons without occupational lead exposure. The levels of lead, cadmium, calcium, iron, copper, magnesium, manganese and zinc were determined by atomic absorption spectrometry (AAS) in whole-blood, erythrocytes, as well as in plasma. The median of the lead-concentration in whole blood of the exposed group was 646 micrograms/l (+/- 66.6%-range: 449-814 micrograms/l). For the normal persons a median of 148 micrograms Pb/l (+/- 66.6%-range: 107-235 micrograms Pb/l) was calculated. In whole-blood, erythrocytes and plasma all element-concentrations of the non-exposed persons were in the normal ranges. The lead-exposed workers showed a higher manganese level. The other elements were found in normal values for this group. Increasing lead-concentrations in blood correlated with elevated levels of manganese and zinc in whole-blood, erythrocytes and plasma. The lead workers showed for the whole-blood manganese concentration a median of 14.2 micrograms/l (+/- 66.6%-range: 8.5-22.3 micrograms/l), for zinc a median of 6.3 mg/l (+/- 66.6%-range: 5.2-8.2 mg/l). Those levels were significantly higher than the levels of the non-exposed persons. For this group the median concentration of manganese was 4.8 micrograms/l (+/- 66.6%-range: 2.7-8.6 micrograms/l) and 5.7 mg/l (+/- 66.6%-range: 5.1-6.3 mg/l) for zinc respectively. For zinc positive correlation between blood lead levels and the levels of manganese and zinc in the three blood-compartments was found. An essential change of the element concentrations between erythrocytes and plasma, in the sense of a displacement from one blood-compartment to the other could not be detected.

In vivo evaluation of epidermal growth factor (EGF) receptor density on human tumor xenografts using radiolabeled EGF and anti-(EGF receptor) mAb 425.

In order to study the potential of non-invasive scintigraphic evaluation of the epidermal growth factor (EGF) receptor status in vivo, the biokinetics and tumor binding of 125I-EGF and anti-(EGF receptor) mAb 425 were investigated in nude mice bearing human tumor xenografts with different EGF-receptor densities as determined by a radioreceptor assay. The results demonstrated a tumor uptake for both substances depending on the receptor level. The EGF receptor status, however, was reflected slightly better by the binding of EGF to tumor tissue compared to the mAb. The rapid blood clearance of EGF with a plasma half-life of less than 1 min led to a tumor-to-blood ratio of approximately 3 within 6 h after injection in tumors with a high receptor expression. A similar ratio for the mAb was not obtained before day 6 after injection. The absolute concentration of EGF, however, was low compared to the mAb. Therefore, it can be concluded that the EGF receptor status as a target for (radio)immunotherapy can be evaluated in vivo with EGF labeled with a short-life positron-emitting radionuclide or with monoclonal antibodies to the EGF receptor or their fragments.

Assessment of a theoretical formalism for dose estimation in CT: an anthropomorphic phantom study.

Dose assessment in computed tomography (CT) is challenging due to the vast variety of CT scanners and imaging protocols in use. In the present study, the accurateness of a theoretical formalism implemented in the PC program CT-EXPO for dose calculation was evaluated by means of phantom measurements. Phantom measurements were performed with four 1-slice, four 4-slice and two 16-slice spiral CT scanners. Firstly, scanner-specific nCTDIw values were measured and compared with the corresponding standard values used for dose calculation. Secondly, effective doses were determined for three CT scans (head, chest and pelvis) performed at each of the ten installations from readings of thermoluminescent dosimeters distributed inside an anthropomorphic Alderson phantom and compared with the corresponding dose values computed with CT-EXPO. Differences between standard and individually measured nCTDIw values were less than 16%. Statistical analysis yielded a highly significant correlation (P < 0.001) between calculated and measured effective doses. The systematic and random uncertainty of the dose values calculated using standard nCTDIw values was about -9 and +/- 11%, respectively. The phantom measurements and model calculations were carried out for a variety of CT scanners and representative scan protocols validate the reliability of the dosimetric formalism considered-at least for patients with a standard body size and a tube voltage of 120 kV selected for the majority of CT scans performed in our study.