Synthesis and body distribution of alpha-aminoisobutyric acid-L-11C in normal and prostate cancer-bearing rat after chemotherapy

Dunzendorfer, U; Schmall, Bernard; Bigler, Rodney E.; Zanzonico, Pat; Conti, Peter S.; Dahl, Jan; Kleinert, Edward L.; Whitmore, Willet F.

doi:10.1007/bf00255888

Cited by 35 publications

(13 citation statements)

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“…Modified amino acids have been known as a "non-metabolizable amino acid" with selective affinity for membrane transport system.l 6,17 Also in nuclear medicine, some modified amino acid radiopharmaceuticals, such as [1 -11 C]-aminocyclopentancarboxylic acid18, l9 and [1 -11 C]-alpha-aminoisobutylic acid, 20 have been developed and amino acid transport measurement in vivo has been attempted.21 However, since cyclotron-produced ultra short-lived radionuclides are not suitable for routine use, we have sought the development of a radioiodinated amino acid labeled with 123 I, which can be widely used and offers good physical characteristics for nuclear medicine. In spite of iodination and alpha-methylation of L-tyrosine, I-L-AMT showed high pancreas selectivity in both in vitro and in vivo studies (Figs.…”

Section: Discussionmentioning

confidence: 99%

An artificial amino acid radiopharmaceutical for single photon emission computed tomographic study of pancreatic amino acid transports123I-3-iodo-alpha-methyl-L-tyrosine

et al. 1992

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123I-3-iodo-alpha-methyl-L-tyrosine (123I-L-AMT) was selected and its characteristics on pancreas accumulation, metabolic selectivity and metabolic stability of 125I-L-AMT were studied. The studies on rat tissue slice as well as mouse biodistribution proved very high accumulation of 125I-labeled L-AMT in the pancreas, which was remarkably inhibited by the active transport inhibitor, ouabain. 125I-L-AMT does not enter into protein synthesis and general amino acid catabolism. Moreover, 125I-L-AMT was very stable against enzymatic deiodination. Thus, the above studies indicated that the 123I-labeled L-AMT was an "artificial amino acid" radiopharmaceutical to be used for the selective measurement of the membrane amino acid transport rate in the pancreas.

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Section: Discussionmentioning

confidence: 99%

An artificial amino acid radiopharmaceutical for single photon emission computed tomographic study of pancreatic amino acid transports123I-3-iodo-alpha-methyl-L-tyrosine

et al. 1992

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“…120 Finally, 11 C and 18 F system A transport radiotracers are being studied in the preclinical setting of prostate cancer in preparation for human translation. 46, 121, 122 …”

Section: Other Emerging Pet Radiotracersmentioning

confidence: 99%

PET Tracers Beyond FDG in Prostate Cancer

Schuster

Nanni

Fanti

2016

Seminars in Nuclear Medicine

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Conventional anatomic imaging with computed tomography (CT) and magnetic resonance imaging (MRI) has limitations in the evaluation of prostate cancer. Positron emission tomography (PET) is a powerful imaging technique which can be directed toward molecular targets as diverse as glucose metabolism, density of prostate specific membrane antigen (PSMA) receptors, and skeletal osteoblastic activity. While 2-deoxy-2-[18F]fluorodeoxyglucose (FDG) PET is the mainstay of molecular imaging, FDG has limitations in typically indolent prostate cancer. Yet, there are many useful and emerging PET tracers beyond FDG which provide added value. These include radiotracers interrogating prostate cancer via molecular mechanisms related to the biology of choline, acetate, amino acids, bombesin, dihydrotestosterone, among others. Choline is utilized for cell membrane synthesis and its metabolism is upregulated in prostate cancer. 11C-choline and 18F-choline are in wide clinical use outside the United States, and have proven most beneficial for detection of recurrent prostate cancer. 11C-acetate is an indirect biomarker of fatty acid synthesis which is also upregulated in prostate cancer. Imaging of prostate cancer with 11C-acetate is overall similar to the choline radiotracers yet is not as widely utilized. Upregulation of amino acid transport in prostate cancer provides the biologic basis for amino acid based radiotracers. Most recent progress has been made with the non-natural alicyclic amino acid analogue radiotracer anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid (FACBC or fluciclovine) also proven most useful for the detection of recurrent prostate cancer. Other emerging PET radiotracers for prostate cancer include the bombesin group directed to the gastrin releasing peptide receptor (GRPR), 16β-18F-fluoro-5α-dihydrotestosterone (FDHT) which binds to the androgen receptor, and those targeting the vasoactive intestinal polypeptide receptor 1 (VPAC-1) and urokinase plasminogen activator receptor (uPAR) which are also overexpressed in prostate cancer.

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“…The development of fluorinated methionine and tryptophan derivatives has been reported (62)(63)(64). In addition, 11 C and 18 F system A transport radiotracers have been tested in preclinical prostate cancer animal models and are in the early stages of human translation (3,65,66). A homolog of 18 F-fluciclovine, anti-1-amino-2-18 F-fluorocyclopentane-1-carboxylic acid ( 18 F-FACPC), had been evaluated as a prostate cancer imaging agent in humans.…”

Section: Emerging Amino Acid-based Pet Radiotracersmentioning

confidence: 99%

Evaluation of Prostate Cancer with Radiolabeled Amino Acid Analogs

2016

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Conventional imaging of prostate cancer has limitations related to the frequently indolent biology of the disease. PET is a functional imaging method that can exploit various aspects of tumor biology to enable greater detection of prostate cancer than can be provided by morphologic imaging alone. Radiotracers that are in use or under investigation for targeting salient features of prostate cancer include those directed to glucose, choline, acetate, prostate-specific membrane antigen, bombesin, and amino acids. The tumor imaging features of this last class of radiotracers mirror the upregulation of transmembrane amino acid transport that is necessary in carcinomas because of increased amino acid use for energy requirements and protein synthesis. Natural and synthetic amino acids radiolabeled for PET imaging have been investigated in prostate cancer patients. Early work with naturally occurring amino acid-derived radiotracers, such as L-11 C-methionine and L-1-11 C-5-hydroxytryptophan, demonstrated promising results, including greater sensitivity than 18 F-FDG for intraprostatic and extraprostatic cancer detection. However, limitations with naturally occurring amino acid-derived compounds, including metabolism of the radiotracer itself, led to the development of synthetic amino acid radiotracers, which are not metabolized and therefore more accurately reflect transmembrane amino acid transport. Of the synthetic amino acid-derived PET radiotracers, anti-1-amino-3-18 F-fluorocyclobutane-1-carboxylic acid ( 18 F-FACBC or 18 F-fluciclovine) has undergone the most promising translation to human use, including the availability of simplified radiosynthesis. Several studies have indicated advantageous biodistribution in the abdomen and pelvis with little renal excretion and bladder activity-characteristics beneficial for prostate cancer imaging. Studies have demonstrated improved lesion detection and diagnostic performance of 18 F-fluciclovine in comparison with conventional imaging, especially for recurrent prostate cancer, although issues with nonspecific uptake limit the potential role of 18 F-fluciclovine in the diagnosis of primary prostate cancer. Although work is ongoing, recently published intrapatient comparisons of 18 F-fluciclovine with 11 C-choline reported higher overall diagnostic performance of the former, especially for the detection of disease relapse. This review is aimed at providing a detailed overview of amino acid-derived PET compounds that have been studied for use in prostate cancer imaging.

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Synthesis and body distribution of alpha-aminoisobutyric acid-L-11C in normal and prostate cancer-bearing rat after chemotherapy

Cited by 35 publications

References 1 publication

An artificial amino acid radiopharmaceutical for single photon emission computed tomographic study of pancreatic amino acid transports123I-3-iodo-alpha-methyl-L-tyrosine

An artificial amino acid radiopharmaceutical for single photon emission computed tomographic study of pancreatic amino acid transports123I-3-iodo-alpha-methyl-L-tyrosine

PET Tracers Beyond FDG in Prostate Cancer

Evaluation of Prostate Cancer with Radiolabeled Amino Acid Analogs

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