Synthesis and evaluation of [18F]1-amino-3-fluorocyclobutane-1-carboxylic acid to image brain tumors.

UNLABELLED We have developed a new tumor-avid amino acid, 1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC), labeled with 18F for nuclear medicine imaging. METHODS [18F]FACBC was prepared with high specific activity (no carrier added [NCA]) and was evaluated for its potential in tumor localization. A comparative study was performed for [18F]FACBC and [18F]2-fluorodeoxyglucose (FDG) in which the uptake of each agent in 9L gliosarcoma (implanted intracerebrally in Fisher 344 rats) was measured. In addition, the first human PET study of [18F]FACBC was performed on a patient with residual glioblastoma multiforme. Quantitative brain images of the patient were obtained by using a Siemens 921 47-slice PET imaging system. RESULTS In the rat brain, the initial level of radioactivity accumulation after injection of [18F]FACBC was low (0.11 percentage injected dose per gram [%ID/g]) at 5 min and increased slightly to 0.26 %ID/g at 60 min. The tumor uptake exhibited a maximum at 60 min (1.72 %ID/g), resulting in a tumor-to-brain ratio increase of 5.58 at 5 min to 6.61 at 60 min. In the patient, the uptake of [18F]FACBC in the tumor exhibited a maximum concentration of 146 nCi/mL at 35 min after injection. The uptake of radioactivity in the normal brain tissue was low, 21 nCi/mL at 15 min after injection, and gradually increased to 29 nCi/mL at 60 min after injection. The ratio of tumor to normal tissue was 6 at 20 min after injection. The [18F]FACBC PET scan showed intense uptake in the left frontal region of the brain. CONCLUSION The amino acid FACBC can be radiofluorinated for clinical use. [18F]FACBC is a potential PET tracer for tumor imaging.

[1]  Arvid Lundervold,et al.  Advances in medical imaging , 1998, Proceedings. Fourteenth International Conference on Pattern Recognition (Cat. No.98EX170).

[2]  O. Schober,et al.  Iodine-123-alpha-methyl tyrosine in gliomas: correlation with cellular density and proliferative activity. , 1997, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[3]  D. Kinzel,et al.  Fluorine-18-FDG PET and iodine-123-IMT SPECT in the evaluation of brain tumors. , 1997, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[4]  David J. Yang,et al.  Comparison of fluorine-18-fluorodeoxyglucose and carbon-11-methionine PET in detection of malignant tumors. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[5]  R. Maciunas,et al.  Optimal cutoff levels of F-18 fluorodeoxyglucose uptake in the differentiation of low-grade from high-grade brain tumors with PET. , 1995, Radiology.

[6]  F. Shishido,et al.  Perfusion and metabolism in predicting the survival of patients with cerebral gliomas , 1994, Cancer.

[7]  J. S. Laughlin,et al.  Tumor imaging with carbon-11 labeled alpha-aminoisobutyric acid (AIB) in patients with malignant melanoma. , 1991, American journal of physiologic imaging.

[8]  K Wienhard,et al.  Increased amino acid transport into brain tumors measured by PET of L-(2-18F)fluorotyrosine. , 1991, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[9]  F. Shishido,et al.  Clinical Value of Pet with 18F-Fluorodeoxyglucose and L-Methyl-11C-Methionine for Diagnosis of Recurrent Brain Tumor and Radiation Injury , 1991, Acta radiologica.

[10]  J M Hoffman,et al.  Clinical application of PET for the evaluation of brain tumors. , 1991, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[11]  L G Strauss,et al.  The applications of PET in clinical oncology. , 1991, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[12]  P. Conti,et al.  Advances in medical imaging for cancer diagnosis and treatment , 1991, Cancer.

[13]  Alan C. Evans,et al.  Metabolic and hemodynamic evaluation of gliomas using positron emission tomography. , 1987, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[14]  G. Chiro Positron emission tomography using [18F] fluorodeoxyglucose in brain tumors. A powerful diagnostic and prognostic tool. , 1987 .

[15]  R. Beaney Positron emission tomography in the study of human tumors. , 1984, Seminars in nuclear medicine.

[16]  R A Brooks,et al.  Glucose utilization of cerebral gliomas measured by [18F] fluorodeoxyglucose and positron emission tomography , 1982, Neurology.

[17]  W. D. Gibbs,et al.  Brain Tumor Imaging by Positron Emission Computed Tomography Using 11C‐Labeled Amino Acids , 1982, Journal of computer assisted tomography.

[18]  R. Hayes,et al.  1-aminocyclobutane[11C]carboxylic acid, a potential tumor-seeking agent. , 1979, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[19]  G. Goldstein,et al.  Polarity of the blood-brain barrier: neutral amino acid transport into isolated brain capillaries. , 1978, Science.

[20]  J. Anon,et al.  Effect of structure on tumor specificity of alicyclic alpha-amino acids. , 1978, Cancer research.

[21]  W. S. Snyder,et al.  Dose to the fetus from radionuclides in the bladder. , 1973, Health physics.

[22]  R. W. Holley A unifying hypothesis concerning the nature of malignant growth. , 1972, Proceedings of the National Academy of Sciences of the United States of America.

[23]  W H Oldendorf,et al.  Brain uptake of radiolabeled amino acids, amines, and hexoses after arterial injection. , 1971, The American journal of physiology.

[24]  O. Schober,et al.  Diagnosis of recurrent glioma with SPECT and iodine-123-α-methyl tyrosine , 1998 .

[25]  P. Conti Introduction to imaging brain tumor metabolism with positron emission tomography (PET). , 1995, Cancer investigation.

[26]  M. Goodman,et al.  Microprocessor-controlled open vessel system for the production of no- carrier-added 1-[ 11 C]-1-aminocyclobutane-1-carboxylic acid , 1994 .

[27]  P A Dekker-de Kiefte,et al.  Diagnosis and Treatment , 2020, Diabetes.

[28]  H. Coenen Biochemistry and Evaluation of Fluoroamino Acids , 1993 .

[29]  F Shishido,et al.  Cerebral glioma: evaluation with methionine PET. , 1993, Radiology.

[30]  K. Herholz,et al.  Kinetic Modeling of Fluorotyrosine Uptake , 1993 .

[31]  G. di Chiro Which PET radiopharmaceutical for brain tumors? , 1991, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[32]  K. Eckerman Aspects of the dosimetry of radionuclides within the skeleton with particular emphasis on the active marrow , 1985 .

[33]  P. Conti,et al.  Synthesis and quality assurance of [11C]alpha-aminoisobutyric acid (AIB), a potential radiotracer for imaging and amino acid transport studies in normal and malignant tissues. , 1984, International journal of nuclear medicine and biology.

[34]  Barry H. Smith,et al.  Issues in the in vivo measurement of glucose metabolism of human central nervous system tumors , 1984, Annals of neurology.