0000000000075343
AUTHOR
Alwin E. Goetz
Relation between autoradiographically measured blood flow and ATP concentrations obtained from imaging bioluminescence in tumors following hyperthermia.
The effects of moderate local hyperthermia (43.3 degrees C/30 min) on regional blood flow and regional ATP distribution in the amelanotic hamster melanoma A-Mel-3 were investigated by high-resolution techniques. Blood flow and ATP concentrations were measured simultaneously in treated and untreated tumors and in adjacent tissues by means of (14C)-Iodoantipyrine autoradiography and quantitative imaging bioluminescence in consecutive tissue sections at 3, 12 and 24 hr following treatment. Digital image processing and the use of a special algorithm allowed the regional interrelationship of the 2 parameters to be quantified. Measurements revealed a great heterogeneity of blood flow and ATP betw…
Aufnahme und Phototoxizität von Hämatoporphyrinderivat in normalen und malignen Zellen
Die Photodynamische Therapie (PDT) stellt neben der Chemo-, Radio- und chirurgischen Therapie ein neues alternatives Therapiekonzept in der Behandlung von malignen Tumoren dar. Das Prinzip beruht auf der systemischen Applikation (i.v. Injektion) einer photosensibilisierenden Substanz, z.B. Hamatoporphyrinderivat (HPD), und der nachfolgenden Bestrahlung mit Licht geeigneter Wellenlange, z.B. Laserlicht (630 nm). Fur die tumorselektive Wirkung dieser Therapie werden die selektive Aufnahme bzw. vermehrte Speicherung der photoaktiven Substanzen im Tumorgewebe [1] sowie auch eine im Vergleich zum Normalgewebe erhohte Sensibuitat von Tumorgewebe gegenuber der PDT postuliert. Ungeklart ist, ob die…
Correlation between Regional Atp and Blood Flow in Tumors and Surrounding Normal Tissue
Various experimental and human tumors are characterized by a marked heterogeneity in the pathophysiologic micromilieu (1, 2). An inadequate and heterogeneous nutritional blood supply has been suggested to explain the non-uniform distribution of oxygen, pH, and high energy phosphates as it has been observed by many investigators (3, 4). Although there is a distinct understanding of the general interrelationships between these parameters (5), little is known about their actual regional correlation, which cannot be assessed by global measurements. With the autoradiographic method for measurement of blood flow (6, 7) and the metabolic imaging with ATP-induced bioluminescence (8, 9) it has becom…
An in vitro model to study cellular photosensitizer uptake and photodynamic dose-response relationships of tumor cells
Cellular fluorescence intensity (CFI) after incubation with varying concentrations of the photosensitizer Photofrin and the photodynamically induced dose-response relationships of hamster melanoma cells (A-MEL-3) were studied in a recently developed in vitro model. After administration of Photofrin to the extracellular serum-free medium, CFI was evaluated by flow cytometry together with constantly fluorescing latex particles used as a reference. After 5 min, 50% of maximal CFI was found, and after 60 min CFI was maximal. No further increase was obtained during the exposure to Photofrin over the incubation period of 4 h. During this plateau phase, CFI was significantly related to the concent…
Pixel-to-pixel correlation between images of absolute ATP concentrations and blood flow in tumours
Iodo(14C-)antipyrine autoradiography and imaging bioluminescence have been combined to obtain pixel-to-pixel correlations between absolute values for local blood flow and ATP concentrations at a microscopical level within designated areas in hamster melanomas. Positive pixel-to-pixel correlations were obtained in 4 of 6 tumours. Both flow and ATP values were less in mostly necrotic than in mostly viable tumour regions. The data provide evidence for the energetic state of cancer cells being strongly influenced by the efficiency of tumour microcirculation in several but not in all malignancies investigated. Images Figure 1
Relation of early Photofrin uptake to photodynamically induced phototoxicity and changes of cell volume in different cell lines.
For efficacy of photodynamic therapy, selective uptake and retention of photoactive substances has been postulated. Therefore, measurements were performed to find out whether the photosensitiser Photofrin® is taken up differently in malignant and non-malignant cells in vitro . In addition, the sensitivity of malignant cells and nonmalignant cells to photodynamic exposure was investigated, by quantifying viability and volume alterations of the cells. Bovine aortic endothelial cells, mouse fibroblasts and amelanotic hamster melanoma cells were suspended in a specially designed incubation chamber under controlled conditions (e.g. pH, p O 2 , p CO 2 and temperature). After establishing constant…
In-vitro Untersuchungen zu photodynamisch induzierten Dosis-Wirkungs-Beziehungen
Im Gegensatz zu fruheren Annahmen wurde von Rodgers 1990 in Frage gestellt, das aus der Quantifizierung der Fluoreszenz im Gewebe Aussagen uber die Konzentration des Photosensibilisators noch uber die zu erwartenden photodynami-schen Effekte moglich sind (1).