Skip to main content

The Role of Nuclear Medicine in Relation to Alternative Modalities

  • Chapter
Molecular Nuclear Medicine
  • 260 Accesses

Abstract

Optical imaging techniques such as fluorescent microscopy or bioluminescence have for a long time been used in vitro in molecular biology (Contag et al. 1998; Flotte et al. 1998; Moore et al. 1998 a, b; Simonova et al. 1999). Reporter genes with an optical signature (e.g. fluorescence, bioluminescence) can be linked to genetic regulatory elements that can reveal spatial and temporal information about a variety of biological processes at the level of transcription (Contag et al. 1995, 1998). Several technical advances in the field of photon generation as well as photon detection have opened the door for taking these techniques one step further and probe for optical molecular beacons in vivo. Application of light in the near infrared range (NIR) which travels more efficiently through the tissue-compared visible light (Chance 1998), highly sensitive CCD-technology and various techniques such as phase modulation, ultra-fast imaging with early arriving photons and diffuse optical tomography are currently being explored to apply optical imaging to detection of deeper structures in vivo (Boas et al. 1994; Wu et al. 1997; Chance 1998; Mahmood et al. 1999; Ntziachristos et al. 2000). Recently, diffuse optical tomography has successfully been applied to detect breast lesions in a clinical setting (Ntziachristos et al. 2000). Besides the macroscopic diagnostic level, at the microscopic level, 10 urn resolution is achievable using optical coherence tomography (Boppart et al. 1997; Tearney et al. 1997), a technique analogous to ultrasound. Subsurface imaging of fluorescence (Mahmood et al. 1999; Weissleder et al. 1999) can be brought to the subcellular level in mouse models with intravital microscopy (Fukumura et al. 1998; Monsky et al. 1999; Dellian et al. 2000). Bioluminescence imaging (Contag et al. 1997, 2000; Sweeney et al. 1999) can be used to follow transgene expression in the whole animal, albeit at somewhat lower resolution. Various optical imaging marker genes and optical imaging probes have been developed over the last years and will be briefly discussed in the following sections.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Ahrens ET, Rothbacher U, Jacobs RE et al (1998) A model for MRI contrast enhancement using Tl agents. Proc Natl Acad Sci USA 95:8443–8448

    Article  PubMed  CAS  Google Scholar 

  • Boas DA, O’Leary MA, Chance B et al (1994) Scattering of diffuse photon density waves by spherical inhomogeneities within turbid media: analytic solution and applications. Proc Natl Acad Sci USA 91:4887–4891

    Article  PubMed  CAS  Google Scholar 

  • Boppart SA, Tearney GJ, Bouma BE et al (1997) Noninvasive assessment of the developing Xenopus cardiovascular system using optical coherence tomography. Proc Natl Acad Sci USA 94:4256–4261

    Article  PubMed  CAS  Google Scholar 

  • Bremer C, Tung C, Weissleder R (2001) In vivo molecular target assessment of matrix metalloproteinase inhibition. Nat Med 7:655–656

    Article  Google Scholar 

  • Chalfie M, Tu Y, Euskirchen G et al (1994) Green fluorescent protein as a marker for gene expression. Science 263:802–805

    Article  PubMed  CAS  Google Scholar 

  • Chance B (1998) Near-infrared images using continuous, phase-modulated, and pulsed light with quantitation of blood and blood oxygenation. Ann NY Acad Sci 838:29–45

    Article  PubMed  CAS  Google Scholar 

  • Cole NB, Smith CL, Sciaky N et al (1996) Diffusional mobility of Golgi proteins in membranes of living cells. Science 273:797–801

    Article  PubMed  CAS  Google Scholar 

  • Contag CH, Contag PR, Mullins JI et al (1995) Photonic detection of bacterial pathogens in living hosts. Mol Microbiol18:593–603

    Google Scholar 

  • Contag CH, Spilman SD, Contag PR et al (1997) Visualizing gene expression in living mammals using a bioluminescent reporter. Photochem Photobiol 66:523–531

    Article  PubMed  CAS  Google Scholar 

  • Contag CH, Jenkins D, Contag PR et al (2000) Use of reporter genes for optical measurements of neoplastic disease in vivo (in process citation). Neoplasia 2:41–52

    Article  PubMed  CAS  Google Scholar 

  • Contag PR, Olomu IN, Stevenson DK et al (1998) Bioluminescent indicators in living mammals. Nat Med 4:245–247

    Article  PubMed  CAS  Google Scholar 

  • Cotten M, Wagner E, Birnstiel ML (1993) Receptor-mediated transport of DNA into eukaryotic cells. Methods Enzymol 217:618–644

    Article  PubMed  CAS  Google Scholar 

  • Dellian M, Yuan F, Trubetskoy VS et al (2000) Vascular permeability in a human tumour xenograft: molecular charge dependence. Br J Cancer 82:1513–1518

    Article  PubMed  CAS  Google Scholar 

  • Edinger M, Sweeney TJ, Tucker AA et al (1999) Noninvasive assessment of tumor cell proliferation in animal models. Neoplasia 1:303–310

    Article  PubMed  CAS  Google Scholar 

  • Edwards DR, Murphy G (1998) Cancer. Proteases—invasion and more. Nature 394:527–528

    Article  PubMed  CAS  Google Scholar 

  • Enochs WS, Hyslop WB, Bennett HF et al (1989) Sources of the increased longitudinal relaxation rates observed in melanotic melanoma. An in vitro study of synthetic melanins. Invest Radiol 24:794–804

    Article  PubMed  CAS  Google Scholar 

  • Enochs WS, Petherick P, Bogdanova A et al (1997) Paramagnetic metal scavenging by melanin: MR imaging. Radiology 204:417–423

    PubMed  CAS  Google Scholar 

  • Fang J, Shing Y, Wiederschain D et al (2000) Matrix metal-loproteinase-2 is required for the switch to the angiogenic phenotype in a tumor model. Proc Natl Acad Sci USA 97:3884–3889

    Article  PubMed  CAS  Google Scholar 

  • Flotte TR, Beck SE, Chesnut K et al (1998) A fluorescence video-endoscopy technique for detection of gene transfer and expression. Gene Ther 5:166–173

    Article  PubMed  CAS  Google Scholar 

  • Fukumura D, Xavier R, Sugiura T et al (1998) Tumor induction of VEGF promoter activity in stromal cells. Cell 94:715–725

    Article  PubMed  CAS  Google Scholar 

  • Girotti M, Banting G (1996) TGN38-green fluorescent protein hybrid proteins expressed in stably transfected eukaryotic cells provide a tool for the real-time, in vivo study of membrane traffic pathways and suggest a possible role for ratTGN38. J Cell Sci 109:2915–2926

    PubMed  CAS  Google Scholar 

  • Hickey MJ, Arain TM, Shawar RM et al (1996) Luciferase in vivo expression technology: use of recombinant mycobacterial reporter strains to evaluate antimycobacterial activity in mice. Antimicrob Agents Chemother 40:400–407

    PubMed  CAS  Google Scholar 

  • Isiklar I, Leeds NE, Fuller GN et al (1995) Intracranial metastatic melanoma: correlation between MR imaging characteristics and melanin content. Am J Roentgenol 165:1503–1512

    CAS  Google Scholar 

  • Johnson GA, Benveniste H, Black RD et al (1993) Histology by magnetic resonance microscopy. Magn Reson Q 9:1–30

    PubMed  CAS  Google Scholar 

  • Kayyem JF, Kumar RM, Fraser SE et al (1995) Receptor-targeted co-transport of DNA and magnetic resonance contrast agents. Chem Biol 2:615–620

    Article  PubMed  CAS  Google Scholar 

  • Koretsky A, Lin Y, Schorle H et al (1996) Genetic control of MRI contrast by expression of the transferrin receptor. Int Symp Magn Reson Med, New York, p 5471

    Google Scholar 

  • Kwon BS, Haq AK, Kim GS et al (1988) Cloning and characterization of a human tyrosinase cDNA. Prog Clin Biol Res 256:273–282

    PubMed  CAS  Google Scholar 

  • Louie AY, Huber MM, Ahrens ET et al (2000) In vivo visualization of gene expression using magnetic resonance imaging. Nat Biotechnol 18:321–325

    Article  PubMed  CAS  Google Scholar 

  • Mahmood U, Tung CH, Bogdanov A Jr et al (1999) Near-infrared optical imaging of protease activity for tumor detection. Radiology 213:866–870

    PubMed  CAS  Google Scholar 

  • Matz MV, Fradkov AF, Labas YA et al (1999) Fluorescent proteins from nonbioluminescent Anthozoa species (see comments; published erratum appears in Nat Biotechnol 1999, 17:1227. Nat Biotechnol 17:969–973

    Article  PubMed  CAS  Google Scholar 

  • Monsky WL, Fukumura D, Gohongi T et al (1999) Augmentation of transvascular transport of macromolecules and nanoparticles in tumors using vascular endothelial growth factor. Cancer Res 59:4129–4135

    PubMed  CAS  Google Scholar 

  • Moore A, Sergeyev N, Bredow S et al (1998 a) A model system to quantitate tumor burden in locoregional lymph nodes during cancer spread. Invasion Metastasis 18:192–197

    Article  PubMed  Google Scholar 

  • Moore A, Marecos E, Simonova M et al (1998 b) Novel gliosarcoma ell line expressing green fluorescent protein: a model for quantitative assessment of angiogenesis. Microvasc Res 56:145–153

    Article  PubMed  CAS  Google Scholar 

  • Moore A, Basilion JP, Chiocca EA et al (1998 c) Measuring transferrin receptor gene expression by NMR imaging. Biochim Biophys Acta 1402:239–249

    Article  PubMed  CAS  Google Scholar 

  • Morrey JD, Bourn SM, Bunch TD et al (1991) In vivo activation of human immunodeficiency virus type 1 long terminal repeat by UV type A (UV-A) light plus psoralen and UV-B light in the skin of transgenic mice. J Virol 65:5045–5051

    PubMed  CAS  Google Scholar 

  • Nelson AR, Fingleton B, Rothenberg ML et al (2000) Matrix metalloproteinases: biologic activity and clinical implications. J Clin Oncol 18:1135–1149

    PubMed  CAS  Google Scholar 

  • Ntziachristos V, Yodh AG, Schnall M et al (2000) Concurrent MRI and diffuse optical tomography of breast after indocyanine green enhancement. Proc Natl Acad Sci USA 97:2767–2772

    Article  PubMed  CAS  Google Scholar 

  • Okazaki M, Kuwata K, Miki Y et al (1985) Electron spin relaxation of synthetic melanin and melanin-containing human tissues as studied by electron spin echo and electron spin resonance. Arch Biochem Biophys 242:197–205

    Article  PubMed  CAS  Google Scholar 

  • Prasher DC, Eckenrode VK, Ward WW et al (1992) Primary structure of the Aequorea victoria green-fluorescent protein. Gene 111:229–233

    Article  PubMed  CAS  Google Scholar 

  • Presley JF, Cole NB, Schroer TA et al (1997) ER-to-Golgi transport visualized in living cells (see comments). Nature 389:81–85

    Article  PubMed  CAS  Google Scholar 

  • Simonova M, Weissleder R, Sergeyev N et al (1999) Targeting of green fluorescent protein expression to the cell surface. Biochem Biophys Res Commun 262:638–642

    Article  PubMed  CAS  Google Scholar 

  • Simonova M, Wall A, Weissleder R et al (2000) Tyrosinase mutants are capable of prodrug activation in transfected non-melanotic cells. Cancer Res 60:6656–6662

    PubMed  CAS  Google Scholar 

  • Siragusa GR, Nawotka K, Spilman SD et al (1999) Real-time monitoring of Escherichia coli O157-.H7 adherence to beef carcass surface tissues with a bioluminescent reporter. Appl Environ Microbiol 65:1738–1745

    PubMed  CAS  Google Scholar 

  • Smith BR, Johnson GA, Groman EV et al (1994) Magnetic resonance microscopy of mouse embryos. Proc Natl Acad Sci USA 91:3530–3533

    Article  PubMed  CAS  Google Scholar 

  • Stegman LD, Rehemtulla A, Beattie B et al (1999) Noninvasive quantitation of cytosine deaminase transgene expression in human tumor xenografts with in vivo magnetic resonance spectroscopy. Proc Natl Acad Sci USA 96:9821–9826

    Article  PubMed  CAS  Google Scholar 

  • Sweeney TJ, Mailander V, Tucker AA et al (1999) Visualizing the kinetics of tumor-cell clearance in living animals. Proc Natl Acad Sci USA 96:12044–12049

    Article  PubMed  CAS  Google Scholar 

  • Tearney GJ, Brezinski ME, Bouma BE et al (1997) In vivo endoscopie optical biopsy with optical coherence tomography (see comments). Science 276:2037–2039

    Article  PubMed  CAS  Google Scholar 

  • Thompson EM, Adenot P, Tsuji FI et al (1995) Real time imaging of transcriptional activity in live mouse preimplantation embryos using a secreted luciferase. Proc Natl Acad Sci USA 92:1317–1321

    Article  PubMed  CAS  Google Scholar 

  • Thorstensen K, Romslo I (1993) The transferrin receptor: its diagnostic value and its potential as therapeutic target. Scand J Clin Lab Invest Suppl 215:113–120

    Article  PubMed  CAS  Google Scholar 

  • Tung CH, Bredow S, Mahmood U et al (1999) Preparation of a cathepsin D sensitive near-infrared fluorescence probe for imaging. Bioconjug Chem 10:892–896

    Article  PubMed  CAS  Google Scholar 

  • Tung C, Mahmood U, Bredow S et al (2000) In vivo imaging of proteolytic activity using a novel molecular reporter. Cancer Res 60:4953–4958

    PubMed  CAS  Google Scholar 

  • Walter G, Barton ER, Sweeney HL (2000) Noninvasive measurement of gene expression in skeletal muscle. Proc Natl Acad Sci USA 97:5151–5155

    Article  PubMed  CAS  Google Scholar 

  • Weissleder R, Simonova M, Bogdanova A et al (1997) MR imaging and scintigraphy of gene expression through melanin induction. Radiology 204:425–429

    PubMed  CAS  Google Scholar 

  • Weissleder R, Tung CH, Mahmood U et al (1999) In vivo imaging of tumors with protease-activated near-infrared fluorescent probes. Nat Biotechnol 17:375–378

    Article  PubMed  CAS  Google Scholar 

  • Weissleder R, Moore A, Mahmood U et al (2000) In vivo magnetic resonance imaging of transgene expression. Nat Med 6:351–355

    Article  PubMed  CAS  Google Scholar 

  • Wu J, Perelman L, Dasari RR et al (1997) Fluorescence tomographic imaging in turbid media using early-arriving photons and Laplace transforms. Proc Natl Acad Sci USA 94:8783–8788

    Article  PubMed  CAS  Google Scholar 

  • Yokoe H, Meyer T (1996) Spatial dynamics of GFP-tagged proteins investigated by local fluorescence enhancement (see comments). Nat Biotechnol 14:1252–1256

    Article  PubMed  CAS  Google Scholar 

  • Zhang L, Hellstrom KE, Chen L (1994) Luciferase activity as a marker of tumor burden and as an indicator of tumor response to antineoplastic therapy in vivo. Clin Exp Metastasis 12:87–92

    Article  PubMed  CAS  Google Scholar 

  • Zhang W, Contag PR, Madan A et al (1999) Bioluminescence for biological sensing in living mammals. Adv Exp Med Biol 471:775–784

    Article  PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Bremer, C., Weissleder, R. (2003). The Role of Nuclear Medicine in Relation to Alternative Modalities. In: Feinendegen, L.E., Shreeve, W.W., Eckelman, W.C., Bahk, YW., Wagner, H.N. (eds) Molecular Nuclear Medicine. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-55539-8_30

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-55539-8_30

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-62427-8

  • Online ISBN: 978-3-642-55539-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics