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.