Simultaneous high-resolution measurement of adenosine triphosphate levels and blood flow in the hamster amelanotic melanoma A-Mel-3.
BACKGROUND
Some studies suggest that nutritional blood flow and intratumor levels of high-energy phosphates such as adenosine triphosphate (ATP) affect tumor response to treatment. Reports of intratumor variabilities have shown that distribution of high-energy phosphates within experimental and human tumors is not uniform, and this variability may be related to differences in blood flow in different regions of the tumor. However, previous studies provide no insight into the intratumor relationship of these parameters.


OBJECTIVE
To study the intratumor relationship between blood flow and ATP concentration, we have developed a method that allows simultaneous quantitation of the two variables almost at a cellular level at adjacent sites. In addition, this technique, which uses digital image processing and analysis, facilitates regional high-resolution measurements of blood flow and ATP concentrations in relation to histology.


METHODS
We examined tissue samples cut in consecutive order from one representative hamster A-Mel-3 amelanotic melanoma. Specimens from the same tumor were analyzed for histological features, blood flow (measured autoradiographically by the use of [4-N-methyl-14C]iodoantipyrine), and ATP content (measured by a quantitative substrate-induced bioluminescence reaction, using single-photon imaging). The data on the three parameters were stored as digitized images, which were later transformed to reach geometric congruency. The relationship between blood flow and ATP was examined by nonlinear regression and correlation analyses.


RESULTS
Regional distribution of blood flow was highly correlated with distribution of ATP within the A-Mel-3 tumor. For images of the tumor using measuring fields of approximately 20 tumor cells, the coefficient of correlation was .92 (P < .001). The relationship between the two parameters was described by a second-order function. At low blood flow values, small differences in blood flow were associated with large changes in levels of ATP, whereas at high blood flow values, differences in blood flow were associated with much smaller changes in ATP levels.


CONCLUSIONS
This high-resolution technique may have applications in future studies investigating the relationship between tumor cell metabolism and regional blood flow and in studies aimed at identifying the locoregional target of various cancer therapies.
Kuhnle
G E
GE
Institute of Surgical Research, Ludwig-Maximilians-Universität, Munich, Federal Republic of Germany.
Dellian
M
M
Walenta
S
S
Mueller-Klieser
W
W
Goetz
A E
AE
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D003198:Computer Simulation; D006224:Cricetinae; D014644:Genetic Variation / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D008297:Male; D008546:Melanoma, Experimental / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008647:Mesocricetus; D008954:Models, Biological; D012039:Regional Blood Flow
D000255:Adenosine Triphosphate