Browse > Article

Radiopharmaceuticals for Imaging of Cellular Proliferation  

Oh, Seung-Jun (Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine)
Publication Information
The Korean Journal of Nuclear Medicine / v.36, no.4, 2002 , pp. 209-223 More about this Journal
Abstract
By considering the biological properties of a tumor, it should be possible to realize better results in cancer therapy. PET imaging offers the opportunity to measure tumor growth non-invasively and repeatedly as an early assessment of response to cancer therapy. Measuring cellular growth instead of energy metabolism showed offer significant advantages in evaluating therapy. Thymidine and its derivative nucleoside compounds can be changed to mono, di- and tri- phosphate compounds by thymidine kinase and then be incorporated into DNA. Their bindings are increased in highly proliferating cells due to the high DNA synthesis rate. To evaluate cell proliferation, many kinds of thymidine and uridine derivatives have been labeled with positron emitter and radioactive iodine. Compared to radiopharmaceuticals which have radioisotope labeled base ring such as pyirmidine, the radiopharmacuticals which have radioisotope labeled sugar ring are more stable in vivo and have metabolic resistance. The biological properties such as DNA incorporation ratios are highly dependent on their chemical structures and metabolic processes. This overview describes synthesis of radiopharmaceuticals and their biological properties for imaging of tumor cell proliferation.
Keywords
Cell proliferation; PET; Positron emitter radioisotope; Radiopharmaceuticals; Nucleoside;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Livingston RE, Hart JS. The clinical applicationof cell kinetics in cancer therapy. Ann Rev Toxicol 1977;17:529-43.
2 Cleaver JE. Thymidine metabolism and cell kinetics. Frontiers Bioi 1967;17:3058-63.
3 Yun MK, Oh SJ, Ha HJ, Ryu JS, Moon DH.High radiochemical yield synthesis of 3'-deoxy3,_[I~fluorothymidine with precursor 5'-O-dimethoxytrityl-2' -deoxy-3' -O-nosyl-b-D-threo-pentofuranosyl thymidine and its 3-N-BOC-protectedanalog. J Nucl Med 2002;43:
4 Shield AF, Grierson JR, Dohmen BM, MachullaHJ, Staynoff JC, Lawhorn-Crews JM, ObradovichJE, Muzik 0, Mangner TJ. Imagingproliferation in vivo with [F-18] FLT andpositron emission tomography. Nat Med 1998;4:1334-6.
5 Abe Y, Fukuda H, Ishiwata K, Yoshioka S,Yamada K, Endo S, Kubota K, Sato T,Matsuzawa T, Takahashi T, Ido T. Studies on18F-labeled pyrimidines. Tumor uptakes of18F-5-fluorouracil, 18F-5-fluoruridine, and 18F_5_fluorodeoxyuridine in animals. Eur J Nucl Med1983;8:258-61.
6 Crawford EJ, Fredkin M, Wolf AP, Flower JS,Gallagher BM, Lambrecht RM, MacGregor RR,Shiue CY, Wondinsky I, Goldin A. 18F_5_Fluorouridine, a new probe for measuring theproliferation of tissue in vivo. Advances inEnzyme Regulation 1982;20:3-22.
7 Alauddin MM, Ravert HT, Musachio JL,Mathews WB, Dannals RF, Conti PS. Selectivealkylation of pyrimidyl dianions III: no-carrieraddedsynthesis of [HC_ methyl]thymidine. NuclMed Bio! 1995;22: 791-94.
8 Bergstrom M, Lu L, Fasth K, Wu F, Bergstrom-Pettermann E, To1machev V, Hedberg E,Cheng A, Langstrom B. In vitro and animalvalidation of bromine-76-bromodeoxyuridine as aproliferation marker. J Nucl Med 1998;39:1273-9.
9 Lu L, Bergstrom M, Fasth K, Wu F, LangstromB. Synthesis of C6Br]bromofluorodeoxyuridineand its validation with regard to uptake, DNAincorporation, and excretion modulation in rats. JNucl Med 2000;41:1746-52.
10 Blasberg RG, Ulrich U, Weinreich R, Beattie B,Ammon K, Yonekawa Y, Landolt H, GuentherI, Crompton NEA, Vontobe1 P, Missimer J,Maguire RP, Koziorowski J, Knust EJ, Finn RD,Leenders KL. Imaging brain tumor proliferativeactivity with C24I]iododeoxyuridine. Cancer Res2000;60: 624-35.
11 Kriss JP, Revesz L. Quatitative studies ofincorporation of exogenous thymidine and 5bromodeoxyuridineinto deoxyribonucleic acid ofmammalian cells in vitro. Cancer Res 1961;21:1141-7.
12 Camochan P, Brooks R. Radio1abelled 5'-iodo2'-deoxyuridine: A promising alternative toC8F]-2-fluoro-2-deoxy-D-g1ucose for PET studiesof early response to anticancer treatment. NuclMed Bioi 1999; 26:667-72.
13 Grierson JR, Shields AF. Radiosynthesis of3' ..deoxy-3' -['sF]fluorothymidine: ['sF]FLT forimaging of cellular proliferation in vivo. NuclMed Bioi 2000;27:143-56.
14 Gambhir SS, Herschman HR, Cherry SR, BarrioJR, Satyamurthy N, Toyokuni T, Phleps ME,Larson SM, Balaton J, Finn R, Sadelain M,Tjuvajev J, Blasberg R. Imaging transgeneexpression with radionuclide imaging technologies.Neoplasia 2000; 2:118-38.
15 Machulla HJ, Blocher A, Kuntzsch M, Piert M,Wei R, Grierson JR. Simplified labeling approachfor synthesizing 3' -deoxy-3' -['sF]fluorothymidine(['sF]FLT). J Radioanal Nucl Chem2000;243:843-6.
16 Carter EA, Mckuster K, Syed S, Tompkins RG,Fischman AJ. Comparison of 18FLT with 18FDGfor differentiation between tumor and focal sitesof infection in rats. J Nucl Med 2002;43:266P.
17 Mankoff DA, Shield AF, Graham MM; LinkJM, Eary JF, Krohn KA. Kinetic analysis of2-[carbon-ll]thymidine PET imaging studies:compartmental model and mathematical analysis.J Nucl Med 1998;39:1043-55.
18 Lu L, Bergstrom M, Fasth K, Wu F, ErikssonB, Langstrom B. Elimination of nonspecificradioactivity from C6Br]bromide in PET studywith C6Br]bromodeoxyuridine. Nucl Med Bioi1999;26:795-802.
19 Ishiwata K, Ido T, Kawashima K, Murakami M,Takahashi T. Studies on 18F-labeled pyrimidines.II. Metabolic investigation of 18F-5-fluorouracil,18F-5-fluoro- 2' -deoxyuridine and 18F-5-fluorouridinein rats. Eur J Nucl Med 1984;9:185-9.
20 Guenther I, Wyer L, Knust EJ, Finn RD, Koziorowski J, Weinreich R, Radiosynthesis and quality control assurance of 5_[1241] iodo-2'-deoxyuridine for functional PET imaging of cell proliferation. Nucl Med Bioi 1998;25:359-65.
21 Shield AF, Mankoff D, Graham MM, Zheng M,Kozawa SM, Link JM, Krohn KA, Analysis of2-carbon-ll-thymidine blood metabolites in PETimaging. J Nucl Med 1996;37:29096.
22 Gardelle 0, Roe1cke U, Vontobe1 P, CromptonNE, Guenther I, Blauenstein P, Schubiger AP,Blattmann H, Ryser JE, Leenders KL, KaserHotz,B. C6Br]Bromodeoxyuridine PET intumor-bearing animals. Nucl Med Bioi 2001;28:51-7.
23 Shield AF, Grierson JR, Kozawa SM, Zheng MDevelopment of labeled thymidine analogs forimaging tumor proliferation. Nucl Med Biol1996;23:17-22.
24 Ishiwata K, Sato K, Kameyama M, YoshimotoT, Ido T. Metabolic fates of 2'-deoxy-5-C8F]fluorouridine in tumor- bearing mice and humanplasm. Nucl Med Bio! 1991;18:539-45.
25 Ishiwata K, Tsurumi Y, Kameyama M, Sato K,Iwata R, Takahashi T, Ido T, Yoshimoto T.Brain tumor accumulation and plasma pharmacokineticparameters of 2;-deoxy-5-18F-fluorouridine.Ann Nucl Med 1993;7:199-205.
26 Krohn KA, Mankoff DA, Eary JF. Imagingcellular proliferation a measure of response totherapy. J Clin Pharmacol 2001;41:96S- 103S.
27 Shield AF, Grierson JR, Muzik 0, Stayanoff JC,Lawhorn-Crews JM, Obradovich JE, MangnerTJ. Kinetics of 3'-deoxy-3'-[F-18]fluorothymidineuptake and retention in dogs. Molecular Imagingand Biology 2002;4:83-9.
28 Steel CJ, Brady F, Luthra SK, Brown G, KhanI, Poole KG, Sergis A, Jones T, Price PM. Anautomated radiosynthesis of 2-[1lC]thymidine usinganhydrous [llC]urea derived from [llC]phosgene.Appl Radiat Isot 1999;51:377-88.
29 Hahn WC, Weinberg RA. Modeling the molecularcircuitry of cancer. Nat Rev Cancer 2002;5:331-41.
30 Martin SJ, Eisenbarth JA, Wagner-Utermann U,Mier W, Henze M, Pritzkow H, Harberkorn U,Eisenhut M. A new precursor for the radiosynthesisof ['sF] FLT. Nucl Med Bioi 2002;29:263-73.
31 Grierson JR, Shield AF, Zheng M, Kozawa SM,Courter JH. Radiosynthesis of labeled bspseudothymidine([C-ll]- and [H-3]methyl) and itsbiodistribution and metabolism in normal andtumored mice. Nucl Med Bio! 1995;22:671-8.
32 Sgouros G, o'Donoghue JA, Larson SM,Macapinlac H, Larson JJ, Kemeny N. Mathematicalmpde1 of 5-C25I]iodo-2'-deoxyuridinetreatment: continuous infusion regimens for hepaticmetastases. Int J Radiation Oncology Bioi Phys1998;41: 1177-83
33 Seitz D, Wagner M, Vogg AT, Glatting G,Neumaier B, Greten FR, Schmid RM, ReskeSN. In vivo evaluation of 5-[18F]fluoro- 2'deoxyuridineas tracer for positron emissiontomography in a murine pancreatic cancermodel. Cancer Res 2001;61:3853-57.
34 Goethals P, Lameire N, Eijkeren M, Kesteloot D,Thierens H, Dams R. [methyl-carbon-ll] Thymidinefor in vivo measurement of cell proliferation.J Nucl Med 1996;37:1048- 52.
35 Goethals P, Lameire L, Eijkeren M, Kesteloot D,Thierens H, Dams R. [methyl-carbon-ll]Thymidinefor in vivo measurement of cell proliferation.J Nucl Med 1996;37:1048- 52.
36 Ryser JE, Blauenstein P, Remy N, Weinreich R,Hasler PH, Novak-Hofer I, Schubiger PA.C6Br]Bromodeoxyuridine, a potential tracer forthe measurement of cell proliferation by positronemission tomography, in vitro and in vivostudies in mice. Nucl Med Bioi 1999;26:673-9.