Radiochemical Synthesis and Evaluation of ¹³N-Labeled 5-Aminolevulinic Acid for PET Imaging of Gliomas

Abstract

The endogenous amino acid, 5-aminolevulinic acid (5-ALA), has received significant attention as an imaging agent, including ongoing clinical trials for image-guided tumor resection due to its selective uptake and subsequent accumulation of the fluorescent protoporphyrin IX in tumor cells. Based on the widely reported selectivity of 5-ALA, a new positron emission tomography imaging probe was developed by reacting methyl 5-bromolevulinate with [N] ammonia. The radiotracer, [N] 5-ALA, was produced in high radiochemical yield (65%) in 10 min and could be purified using only solid phase cartridges. testing in rats bearing intracranial 9L glioblastoma showed peak tumor uptake occurred within 10 min of radiotracer administration. Immunohistochemical staining and fluorescent imaging was used to confirm the tumor location and accumulation of the tracer seen from the PET images. The quick synthesis and rapid tumor specific uptake of [N] 5-ALA makes it a potential novel clinical applicable radiotracer for detecting and monitoring tumors noninvasively.

Synthesis of enantiopure 18F-trifluoromethyl cysteine as a structure-mimetic amino acid tracer for glioma imaging

“…Finally, the desired products 2L and 2D were neutralized (pH ≈ 6) and isolated using solid phase extraction to obtain 14% ± 3% RCY ( n = 6) in 35 min. The radiochemical purity was higher than 98%, as determined by radio-TLC ( Figure S2-3 ) 63. Similar to a previous report about the synthesis of non-radiolabelled L-trifluoromethylcysteine 64, the harsh hydrolysis conditions failed to lead to a β-elimination side reaction, suggesting a good stability of 2L and 2D in acidic conditions.…”

Augmentation of 5-Aminolevulinic Acid Treatment of Glioblastoma by Adding Ciprofloxacin, Deferiprone, 5-Fluorouracil and Febuxostat: The CAALA Regimen

“…The temporal relationship between preferential 5-ALA uptake by glioblastoma cells, within minutes [55], and the later development, within hours [56], of maximal fluorescence—for which PpIX is responsible—suggests that both greater avidity of 5-ALA and stronger weighting of PpIX synthesis are responsible for glioblastoma fluorescence. As discussed above, and evident in the summary Figure 1, CAALA drugs act primarily by enhancing PpIX formation from intracellular 5-ALA and inhibiting further processing or export of PpIX.…”

Synthesis, Radiolabeling, and Biological Evaluation of the trans-Stereoisomers of 1-Amino-3-(fluoro-18F)-4-fluorocyclopentane-1-carboxylic Acid as PET Imaging Agents

“…Anesthesis was carried out as described previously. 33 Rats were anesthetized using isoflurane gas. Anesthesia was initiated 10 min ahead of imaging experiments by placing the animal in a cage ventilated with oxygen containing 1−2% isoflurane.…”

“…The tracer was administered as described previously . A catheter placed in the tail vein prior to imaging experiments was filled with isotonic sodium chloride solution.…”

“…The microPET imaging process was carried out as described previously . After anesthesia and placement of the tail vein catheter, the animal was placed with its body located at the center of the field of view.…”