Abstract
Positron emission tomography (PET) reporter genes (PRGs), when coupled with positron-emitting PET reporter probes (PRPs), are useful for tracking specific cell populations in cell-based therapies, in transgenic animal models, and in xenograft tumor progression experiments. The activities of incorporated PRGs in targeted cells can be monitored noninvasively by PET imaging in preclinical in vivo studies and clinical applications following systemic administration of the appropriate PRG. Here we describe a method that minimizes both design and variability of vector delivery vehicles for alternative PRGs and biological variability of the in vivo target when comparing the efficacy, sensitivity, and specificity of alternative PRG/PRP combinations for in vivo PRG imaging. The principles described for comparing alternative PRG/PRP reporter gene systems can be applied to comparisons of alternative fluorescence, bioluminescence, single-photon emission computerized tomography (SPECT), and magnetic resonance imaging (MRI) reporter genes.
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References
Herschman HR (2004) PET reporter genes for noninvasive imaging of gene therapy, cell tracking and transgenic analysis. Crit Rev Oncol Hematol 51(3):191–204. https://doi.org/10.1016/j.critrevonc.2004.04.006
Iyer M, Sato M, Johnson M, Gambhir SS, Wu L (2005) Applications of molecular imaging in cancer gene therapy. Curr Gene Ther 5(6):607–618
Pysz MA, Gambhir SS, Willmann JK (2010) Molecular imaging: current status and emerging strategies. Clin Radiol 65(7):500–516. https://doi.org/10.1016/j.crad.2010.03.011
Yaghoubi SS, Gambhir SS (2006) PET imaging of herpes simplex virus type 1 thymidine kinase (HSV1-tk) or mutant HSV1-sr39tk reporter gene expression in mice and humans using [18F]FHBG. Nat Protoc 1(6):3069–3075. https://doi.org/10.1038/nprot.2006.459
Berger C, Flowers ME, Warren EH, Riddell SR (2006) Analysis of transgene-specific immune responses that limit the in vivo persistence of adoptively transferred HSV-TK-modified donor T cells after allogeneic hematopoietic cell transplantation. Blood 107(6):2294–2302. https://doi.org/10.1182/blood-2005-08-3503
Gambhir SS, Bauer E, Black ME, Liang Q, Kokoris MS, Barrio JR, Iyer M, Namavari M, Phelps ME, Herschman HR (2000) A mutant herpes simplex virus type 1 thymidine kinase reporter gene shows improved sensitivity for imaging reporter gene expression with positron emission tomography. Proc Natl Acad Sci U S A 97(6):2785–2790
Yaghoubi S, Barrio JR, Dahlbom M, Iyer M, Namavari M, Satyamurthy N, Goldman R, Herschman HR, Phelps ME, Gambhir SS (2001) Human pharmacokinetic and dosimetry studies of [(18)F]FHBG: a reporter probe for imaging herpes simplex virus type-1 thymidine kinase reporter gene expression. J Nucl Med 42(8):1225–1234
Yaghoubi SS, Jensen MC, Satyamurthy N, Budhiraja S, Paik D, Czernin J, Gambhir SS (2009) Noninvasive detection of therapeutic cytolytic T cells with 18F-FHBG PET in a patient with glioma. Nat Clin Pract Oncol 6(1):53–58. https://doi.org/10.1038/ncponc1278
Likar Y, Zurita J, Dobrenkov K, Shenker L, Cai S, Neschadim A, Medin JA, Sadelain M, Hricak H, Ponomarev V (2010) A new pyrimidine-specific reporter gene: a mutated human deoxycytidine kinase suitable for PET during treatment with acycloguanosine-based cytotoxic drugs. J Nucl Med 51(9):1395–1403. https://doi.org/10.2967/jnumed.109.074344
Campbell DO, Yaghoubi SS, Su Y, Lee JT, Auerbach MS, Herschman H, Satyamurthy N, Czernin J, Lavie A, Radu CG (2012) Structure-guided engineering of human thymidine kinase 2 as a positron emission tomography reporter gene for enhanced phosphorylation of non-natural thymidine analog reporter probe. J Biol Chem 287(1):446–454. https://doi.org/10.1074/jbc.M111.314666
Hazra S, Sabini E, Ort S, Konrad M, Lavie A (2009) Extending thymidine kinase activity to the catalytic repertoire of human deoxycytidine kinase. Biochemistry 48(6):1256–1263. https://doi.org/10.1021/bi802062w
Iyidogan P, Lutz S (2008) Systematic exploration of active site mutations on human deoxycytidine kinase substrate specificity. Biochemistry 47(16):4711–4720. https://doi.org/10.1021/bi800157e
Gil JS, Machado HB, Campbell DO, McCracken M, Radu C, Witte ON, Herschman HR (2013) Application of a rapid, simple, and accurate adenovirus-based method to compare PET reporter gene/PET reporter probe systems. Mol Imaging Biol 15(3):273–281. https://doi.org/10.1007/s11307-012-0596-5
Gil JS, Machado HB, Herschman HR (2012) A method to rapidly and accurately compare the relative efficacies of non-invasive imaging reporter genes in a mouse model and its application to luciferase reporters. Mol Imaging Biol 14(4):462–471. https://doi.org/10.1007/s11307-011-0515-1
Sohlenius-Sternbeck AK (2006) Determination of the hepatocellularity number for human, dog, rabbit, rat and mouse livers from protein concentration measurements. Toxicol In Vitro 20(8):1582–1586. https://doi.org/10.1016/j.tiv.2006.06.003
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Xu, S., Herschman, H.R. (2020). Comparison of the Efficacy and Sensitivity of Alternative PET Reporter Gene/PET Reporter Probe Systems That Minimize Biological Variables. In: Basel, M., Bossmann, S. (eds) Cell Tracking. Methods in Molecular Biology, vol 2126. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0364-2_16
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DOI: https://doi.org/10.1007/978-1-0716-0364-2_16
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