Imaging experimental brain tumors with 1-aminocyclopentane carboxylic acid and alpha-aminoisobutyric acid: comparison to fluorodeoxyglucose and diethylenetriaminepentaacetic acid in morphologically defined tumor regions.
The goal of this study was to evaluate the differences and define the advantages of imaging experimental brain tumors in rats with two nonmetabolized amino acids, 1-aminocyclopentane carboxylic (ACPC) acid and alpha-aminoisobutyric (AIB) acid compared with imaging with fluorodeoxyglucose (FDG) or the gallium-diethylenetriaminepentaacetic acid chelate (Ga-DTPA). 1-aminocyclopentane carboxylic acid, AIB, and FDG autoradiograms were obtained 60 minutes after intravenous injection to simulate positron emission tomography (PET) imaging, whereas the Ga-DTPA autoradiograms were obtained 5 or 10 minutes after injection to simulate gadolinium (Gd)-DTPA-enhanced magnetic resonance (MR) images. Three experimental tumors were studied (C6, RG2, and Walker 256) to provide a range of tumor types. Triple-label quantitative autoradiography was performed, and parametric images of the apparent distribution volume (Va, mL/g) for ACPC or AIB, relative glucose metabolism (R, micromol/100 g/min), vascular permeability to Ga-DTPA (K1, microL/min/g), and histology were obtained from the same tissue section. The four images were registered in an image array processor, and regions of interest in tumor and contralateral brain were defined on morphologic criteria (histology) and were transferred to the autoradiographic images. A comparative analysis of all measured values was performed. The location and morphologic characteristics of the tumor had an effect on the images and measurements of Va, R, and K1. Meningeal extensions of all three tumors consistently had the highest amino acid uptake (Va) and vascular permeability (K1) values, and subcortical portions of the tumors usually had the lowest values. Va and R (FDG) values generally were higher in tumor regions with high-cell density and lower in regions with low-cell density. Tumor areas identified as "impending" necrosis on morphologic criteria consistently had high R values, but little or no change in Va or K1. Tumor necrosis was seen consistently only in the larger Walker 256 tumors; low values of R and Va for AIB (less for ACPC) were measured in the necrotic-appearing regions, whereas K1 was not different from the mean tumor value. The highest correlations were observed between vascular permeability (K1 for Ga-DTPA) and Va for AIB in all three tumors; little or no correlation between vascular permeability and R was observed. The advantages of ACPC and AIB imaging were most convincingly demonstrated in C6 gliomas and in Walker 256 tumors. 1-aminocyclopentane was substantially better than FDG or Ga-DTPA for identifying tumor infiltration of adjacent brain tissue beyond the macroscopic border of the tumor; ACPC also may be useful for identifying low-grade tumors with an intact blood-brain barrier. Contrast-enhancing regions of the tumors were visualized more clearly with AIB than with FDG or Ga-DTPA; viable and necrotic-appearing tumor regions could be distinguished more readily with AIB than with FDG. [11C]-labeled ACPC and AIB are likely to have similar advantages for imaging human brain tumors with PET.
Uehara
H
H
Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, U.S.A.
Miyagawa
T
T
Tjuvajev
J
J
Joshi
R
R
Beattie
B
B
Oku
T
T
Finn
R
R
Blasberg
R
R
D000621:Aminoisobutyric Acids / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000378:metabolism; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D006801:Humans; D008297:Male; D009368:Neoplasm Transplantation; D004369:Pentetic Acid / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011920:Rats, Inbred WF; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000621:Aminoisobutyric Acids; D019275:Radiopharmaceuticals; D003515:Cycloleucine; D019788:Fluorodeoxyglucose F18; C100049:2-aminoisobutyric acid; C065594:cispentacin; D004369:Pentetic Acid