PET reporter genes for noninvasive imaging of gene therapy, cell tracking and transgenic analysis.
ABSTRACT Positron-emission tomography (PET) has been used extensively in the clinic for cancer diagnosis, for staging and for monitoring of therapeutic efficacy. PET has not, however, been used extensively in contemporary animal cancer models. Until recently, appropriate instrumentation was not available and the expertise and knowledge necessary to perform PET analyses in murine models has not been widespread. The fabrication of microPET instruments with appropriate resolution for murine experiments has lead to the establishment of non-invasive techniques for functional imaging. The development of "PET reporter genes" whose activity can be monitored in living animals, based on the reporter gene-dependent sequestration of positron-emitting "PET reporter probes," has lead to innovative analyses of gene expression in transgenic animals, to methods to monitor the location, magnitude and duration of expression for gene therapy vectors and to the ability to non-invasively track the targeting, viability and expansion of cellular therapeutics.
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- "SPECT gathers imaging information based on the amount of gamma-emitting radionucleotides that emit a single photon, but it is generally not as sensitive and less quantifiable than PET. PET detects biochemical processes in cells by measuring the positrons emitted by the probe as it decays and collides with electrons in vivo (Doubrovin et al. 2004, Herschman 2004). The PET emissions are two photons released 180° from one another and detected in an array, which measure the volume and concentration of the probe (Blasberg 2002). "
ABSTRACT: Imaging is one of the fastest growing fields of study. New technologies and multimodal approaches are increasing the application of imaging to determine molecular targets and functional processes in vivo. The identification of a specific target, transporter, or biological process using imaging has introduced major breakthroughs to the field of endocrinology primarily utilizing computed tomography, magnetic resonance imaging, ultrasonography, positron emission tomography, single-photon emission computed tomography, and optical imaging. This review provides a general background to the specific developments in imaging that pertains to in vivo function and target identification in endocrine-based diseases.Journal of Molecular Endocrinology 07/2008; 40(6):253-61. DOI:10.1677/JME-07-0170 · 3.62 Impact Factor
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- "Herpes simplex virus (HSV-1) thymidine kinase (TK) has become of great interest in medical research as a suicide or reporter gene in therapeutic or imaging technique  . "
ABSTRACT: Tumor cells transduced with herpes simplex virus thymidine kinase gene has been intensively applied to the field of positron emission tomography via imaging of its substrate. As a pilot synthesis approach, a facial preparation of 5-[125I]iodoarabinosyl uridine starting from commercial available uridine is reported herein. Interestingly, the tin group in 5-trimethylstannyl arabinosyluridine was easily removed during purification. The destannylation through the formation of a six-ligand coordination involving 2'-hydroxyl and tin was thereby proposed.Nuclear Medicine and Biology 05/2006; 33(3):367-70. DOI:10.1016/j.nucmedbio.2005.12.005 · 2.41 Impact Factor
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ABSTRACT: The synthesis and investigation of 5-[125I]iodoindol-3-yl-beta-d-galactopyranoside ([125I]IBDG) as a radioligand for single-photon emission computed tomography (SPECT) imaging of b-galactosidase expression are described. No-carrier-added [125I]IBDG was synthesized by a radioiododestannylation approach in > 75% overall radiochemical yield and > 99% radiochemical purity. [125I]IBDG was evaluated as a substrate using beta-galactosidase-expressing (D54L) and nonexpressing (D54) human glioma cell lines. A 24-hour incubation of this substrate with cultured cells revealed a 6.5-fold greater intracellular trapping of radioactivity in D54L cells compared with D54 cells. Systemic delivery of [125I]IBDG in nude mice bearing D54L tumors failed to show significant trapping of radioactivity within these tumors by SPECT imaging. In contrast, intratumoral injection of the substrate resulted in efficient trapping of radioactivity in D54L tumors but not D54 tumors, resulting in clear SPECT visualization of the former tumor. Based on dynamic SPECT imaging and blood metabolite analysis, we conclude that although [125I]IBDG is an efficient in vivo substrate for beta-galactosidase, its rapid renal clearance hampers its intratumoral availability on systemic administration.Molecular Imaging 08/2008; 7(4):187-97. · 2.19 Impact Factor