PET and SPECT
Assessment of gene function following the completion of human genome sequencing may be done using radionuclide imaging procedures. These procedures are needed for the evaluation of genetically manipulated animals or newly designed biomolecules which require a thorough understanding of physiology, biochemistry and pharmacology. The experimental approaches will involve many new technologies, including in-vivo imaging with SPECT and PET. Nuclear medicine procedures may be applied for the determination of gene function and regulation using established and new tracers or using in-vivo reporter genes, such as genes encoding enzymes, receptors, antigens or transporters. Visualization of in-vivo reporter gene expression can be done using radiolabeled substrates, antibodies or ligands. Combinations of specific promoters and in-vivo reporter genes may deliver information about the regulation of the corresponding genes. Furthermore, protein-protein interactions and the activation of signal transduction pathways may be visualized noninvasively. The role of radiolabeled antisense molecules for the analysis of mRNA content has to be investigated. However, possible applications are therapeutic interventions using triplex oligonucleotides with therapeutic isotopes, which can be brought near to specific DNA sequences to induce DNA strand breaks at selected loci.
After the identification of new genes, functional information is required to investigate the role of these genes in living organisms. This can be done by analysis of gene expression, protein-protein interaction or the biodistribution of new molecules and may result in new diagnostic and therapeutic procedures, which include visualization of and interference with gene transcription, and the development of new biomolecules to be used for diagnosis and treatment. Furthermore, the characterization of tumor cell-specific properties allows the design of new treatment modalities, such as gene therapy, which circumvent resistance mechanisms towards conventional chemotherapeutic drugs.
KeywordsPositron Emission Tomography MIBG Uptake Herpes Simplex Virus Thymidine Kinase Iodide Uptake Sodium Iodide Symporter
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- Cammilleri S, Sangrajrang S, Perdereau B, Brixy F, Calvo F, Bazin H, Magdelenat H (1996) Biodistribution of iodine-125 tyramine transforming growth factor β antisense oligonucleotide in athymic mice with a human mammary tumor xenograft following intratumoral injection. Eur J Nucl Med 23:448–452PubMedCrossRefGoogle Scholar
- Gambhir SS, Barrio JR, Phelps ME, Iyer M, Namavari M, Satyamurthy N, Wu L, Green LA, Bauer E, MacLaren DC, Nguyen K, Berk AJ, Cherry SR, Herschman HR (1999) Imaging adenoviral-directed reporter gene expression in living animals with positron emission tomography. Proc Natl Acad Sci U S A 96:2333–2338PubMedCrossRefGoogle Scholar
- Gati WP, Misra HK, Knaus EE, Wiebe LI (1984) Structural modifications at the 2′ and 3′ positions of some pyrimidine nucleosides as determinants of their interaction with the mouse erythrocyte nucleoside transporter Biochem Pharmacol 33:3325–3331Google Scholar
- Guo J, McLachlan SM, Hutchinson S, Rapoport B (1998) The greater glycan content of recombinant human thyroid peroxidase of mammalian than of insect cell origin facilitates purification to homogeneity of enzymatically protein remaining soluble at high concentration. Endocrinology 139:999–1005PubMedCrossRefGoogle Scholar
- Hustinx R, Shiue CY, Alavi A, McDonald D, Shiue GG, Zhuang H, Lanuti M, Lambright E, Karp JS, Eck S (2001) Imaging in vivo herpes simplex virus thymidine kinase gene transfer to tumour-bearing rodents using positron emission tomography and (18F)FHPG. Eur J Nucl Med 28:5–12PubMedCrossRefGoogle Scholar
- Kaufman KD, Filetti S, Seto P, Rapoport B (1990) Recombinant human thyroid peroxidase generated in eukaryotic cells: a source of specific antigen for the immunological assay of antimicrosomal antibodies in the sera of patients with autoimmune thyroid disease. J Clin Endocrinol Metab 70:724–728PubMedCrossRefGoogle Scholar
- Sieger S, Jiang S, Schönsiegel F et al (2003) Tumour specific activation of the Sodium/Iodide Symporter Gene under Control of the Glucose Transporter Gene 1 Promoter (GTI-1.3). Eur J Nucl Med 30:748–756Google Scholar
- Zinn KR, Buchsbaum DJ, Chaudhuri, TR, Mountz JM, Grizzle WE, Rogers-BE (2000) Noninvasive monitoring of gene transfer using a reporter receptor imaged with a high-affinity peptide radiolabeled with 99 mTc or 188Re. J Nucl Med 41:887–895Google Scholar