Neue PET-Tracer in der Onkologie

Zusammenfassung

PET ist seit den letzten Jahren international sowohl in der Krankenversorgung als auch in der klinisch experimentellen Forschung als etablierte Methode anzusehen. Dies gilt spätestens seit der internationalen Akzeptanz von PET/CT. In dieser Situation hat die Entwicklung und Verfügbarkeit neuer Tracer zur Untersuchung pathophysiologisch relevanter Stoffwechselwege eine Schlüsselrolle erlangt. In Verbindung mit Bildfusion werden alte Tracer wie z. B. [¹⁸F]Fluorid erneut evaluiert. In der onkologischen PET-Anwendung sind Untersuchungen zur Proliferation von Tumoren mit FLT, zum Prostata-Karzinom mit Cholin bzw. [¹⁸F]Cholin-Derivaten, Hypoxie-Messungen mittels [¹⁸F]FMISO bzw. [¹⁸F]FAZA und [⁶⁸Ga]DOTATOC einige der aktuellen Beispiele für Tracer-Entwicklungen von hoher klinischer Relevanz. In allen Fällen sind die radiochemischen und radiopharmazeutischen Arbeiten so weit geführt, dass zuverlässige Routine-Produktionen die Verfügbarkeit dieser Substanzen sicherstellen.

Abstract

In the last years PET founds its break-through world wide as a method both in clinical application and experimental research. That change is particularly illustrated by the international acceptance of PET/CT. In this situation the development and availability of new tracers, indeed, is an issue of great importance as new tracers directly widen the assessment of pathophysiological alterations. Moreover, the possibility of image fusion recently gave new impacts on the re-evaluation of „old” tracers such as [¹⁸F]fluoride. In oncology examples of new and highly promising PET application, tracers of interest are FLT for tumor proliferation, [¹¹C]cholin or ¹⁸F-labelled cholin derivatives for prostate carcinoma, [¹⁸F]FMISO/[¹⁸F]FAZA for hypoxic tumor tissue and [⁶⁸Ga]DOTATOC for neuroendocrine tumors. Most importantly, in all those examples the radiochemical development now reached a level on which reliable syntheses assure availability of the tracers as mandatory for clinical applications.

PET - Cholin - FLT - Fluor-18 - Kohlenstoff-11

PET - choline - FLT - fluorine-18 - carbon-11

Literatur

• 1 Blake G M, Park-Holohan S J, Fogelman I. Quantitative studies of bone in postmenopausal women using ¹⁸F-Fluoride and ^99mTc-Methylene Diphosphonate.  J Nucl Med. 2002;  43 338-345
• 2 De Jong I P, Pruim J, Elsinga P H, Vaalburg W, Mensink H JA. Visualization of Prostate Cancer with 11C-Choline Positron Emission Tomography.  European Urology. 2002;  42 18-23
• 3 DeGrado T R, Coleman R E, Wang S, Baldwin S W, Orr M D, Robertson C N, Polascik T J, Price D T. Synthesis and Evaluation of 18F-labeled Choline as an Oncological Tracer for Positron Emission Tomography: Initial Findings in Prostate Cancer.  Cancer Res. 2000;  61 110-117
• 4 Ebenhan T, Reischl G, Solbach C, Belka C, Aschoff P, Bihl H, Machulla H J. Evaluation of Choline for Visualization of Prostate Cancer with PET/CT and [¹¹C]Choline.  J Cancer Res Clin Oncol. 2004;  130 S111
• 5 Eschmann S M, Paulsen F, Reimold M, Dittmann H, Welz S, Reischl G, Machulla HJ Bares R. Prognostic impact of hypoxia-imaging with ¹⁸F-Misonidazole-PET in non-small cell lung cancer and head-and-neck cancer prior to radiotherapy.  J Nucl Med. 2004 (akzeptiert); 
• 6 Fazio F, Picchio M, Messa C. Is 11C-choline the most appropriate tracer for prostate cancer? For.  Eur J Nucl Med Mol Imaging. 2004;  31 753-756
• 7 Fricke E, Machtens S, Hofmann M, den Hoff J van, Bergh S, Brunkenhorst T, Meyer G J, Karstens J H, Knapp W H, Boener A R. Positron emission tomography with ¹¹C-acetate and ¹⁸F-FDG in prostate cancer patients.  Eur J Nucl Med Mol Imaging. 2003;  30 607-611
• 8 Hara T, Kosaka N, Kishi H. Development of ¹⁸F-Fluoroethycholine for Cancer Imaging with PET: Synthesis, Biochemistry, and Prostate Cancer Imaging.  J Nucl Med. 2002;  43 187-199
• 9 Hara T, Kosaka N, Kondo S, Kondo T. PET Imaging of Prostate Cancer Using Carbon-11-Choline.  J Nucl Med. 1998;  39 990-995
• 10 Heiss P, Mayer S, Herz M, Wester H J, Schwaiger M, Senekowitsch-Schmidtke R. Investigation of transport mechanism and uptake kinetics of O-(2[¹⁸F]fluoroethyl)-L-tyrosine in vitro and in vivo.  J Nucl Med. 1999;  40 1367-1373
• 11 Henze M, Schuhmacher J, Hipp P, Kowalski J, Becker D W, Doll J, Macke H R, Hofmann M, Debus J, Haberkorn U. PET imaging of somatostatin receptors using [⁶⁸Ga]-DOTA-D-Phe¹-Tyr³-octreotide (DOTATOC): first results in meningioma patients.  J Nucl Med. 2001;  42 1053-1056
• 12 Hetzel M, Arslandemir C, Konig H H, Buck A K, Nussle K, Glatting G, Gabelmann A, Hetzel J, Hombach V, Schirrmeister H. F-18 NaF PET for detection of bone metastases in lung cancer: accuracy, cost-effectiveness, and impact on patient management.  J Bone Miner Res. 2003;  18 2206-2214
• 13 Hofmann M, Maecke H, Borner R, Weckesser E, Schoffski P, Oei L, Schumacher J, Henze M, Heppeler A, Meyer J, Knapp H. Biokinetics and imaging with the somatostatin receptor PET radioligand (⁶⁸)Ga-DOTATOC: preliminary data.  Eur J Nucl Med. 2001;  28 1751-1757
• 14 Hustinx R, Lemaire C, Jerusalem G, Moreau P, Cataldo D, Duysinx B, Aerts J, Fassotte M F, Foidart J, Luxen A. Whole-body tumor imaging using PET and 2-¹⁸F-fluoro-L-tyrosine: preliminary evaluation and comparison with ¹⁸F-FDG.  J Nucl Med. 2003;  44 533-539
• 15 Ishiwata K, Kubota K, Murakami M, Kubota R, Sasaki T, Ishii S, Senda M. Re-evaluation of amino acid PET studies: can the protein synthesis rates in brain and tumor tissues be measured in vivo?.  J Nucl Med. 1993;  34 1936-1943
• 16 Kim S, Chung J K, Im S H, Jeong J M, Lee D S, Kim D G, Jung H W, Lee M C. (¹¹)C-methionine PET as a prognostic marker in patients with glioma: comparison with (¹⁸)F-FDG PET.  Eur J Nucl Med Mol Imaging. 2005;  32 52-59
• 17 Kotzerke J, Prang J, Neumaier B, Volkmer B, Guhlmann A, Kleinschmidt K, Hautmann R, Reske S N. Experience with carbon-11 choline positron emission tomography in prostate carcinoma.  J Nucl Med. 2000;  27 1415-1419
• 18 Kotzerke J, Volkmer B G, Glatting G, van den Hoff J, Gschwend J E, Messer P, Reske S N, Neumaier B. Intraindividual comparison of [¹¹C]acetate and [¹¹C]choline PET for detection of metastases of prostate cancer.  Nuklearmedizin. 2003;  42 25-30
• 19 Kowalski J, Henze M, Schuhmacher J, Macke H R, Hofmann M, Haberkorn U. Evaluation of positron emission tomography imaging using [⁶⁸Ga]-DOTATOC in comparison to [¹¹¹In]-DTPAOC SPECT. First results in patients with neuroendocrine tumors.  Mol Imaging Biol. 2003;  5 42-48
• 20 Machulla H J. Imaging of Hypoxia. (Developments in Nuclear Medicine 33), Kluwer Academic Publisher, Dordrecht 1999
• 21 Oyama N, Akino H, Kanamura H, Suzuki Y, Muramatio S, Yonekura Y, Sadato N, Yamamoto K, Okada K. ¹¹C-Acetate PET Imaging of Prostate Cancer.  J Nucl Med. 2002;  43 181-186
• 22 Piert M, Machulla H J, Becker G, Aldinger P, Winter E, Bares R. Dependency of the [¹⁸F]fluoromisonidazole uptake on oxygen delivery and tissue oxygenation in the porcine liver.  Nucl Med Biol. 2000;  27 693-700
• 23 Reischl G, Bieg C, Schmiedl O, Solbach C, Machulla H J. Highly Efficient Automated Synthesis of [¹¹C]Choline for Multi Dose Utilization.  Appl Radiat Isot. 2004;  60 835-838
• 24 Schirrmeister H, Guhlmann A, Elsner K, Kotzerke J, Glatting G, Rentschler M, Neumaier B, Trager H, Nussle K, Reske S N. Sensitivity in detecting osseous lesions depends on anatomical localization: planar bone scintigraphy vs. ¹⁸F-PET.  J Nucl Med. 1999;  40 1623-1629
• 25 Shields A F, Grierson J R, Dohmen B M, Machulla H J, Stayanoff J C, Lawhorn-Crews J M, Obradovich J E, Muzik O, Manger T J. Imaging Proliferation In Vivo with [F-18] FLT and Positron Emission Tomography (PET).  Nat Med. 1998;  4 1334-1336
• 26 Shreve P, Chiao P C, Humes H D, Schwaiger M, Gross M D. Carbon-11-Acetate PET Imaging in Renal Disease.  J Nucl Med. 1995;  36 1595-1601
• 27 Wolf A P, Redvanly C S. Carbon-11 and radiopharmaceuticals.  Int J Appl Radiat Isot. 1977;  28 29-48
• 28 Yoshimoto M, Waki A, Obata A, Furukawa T, Yonekura Y, Fujibayashi Y. Radiolabeled choline as a proliferation marker: comparison with radiolabeled acetate.  Nucl Med Biol. 2004;  31 859-865
• 29 Yoshimoto M, Waki A, Yonekura Y, Sadato N, Murata T, Omata N, Takahashi N, Welch M J, Fujibayashi Y. Characterization of acetate metabolism in tumor cells in relation to cell proliferation: Acetate metabolism in tumor cells.  Nucl Med Biol. 2001;  28 117-122
• 30 Zöphel K, Kotzerke J. Is ¹¹C-choline the most appropriate tracer for prostate cancer? Against.  Eur J Nucl Med Mol Imaging. 2004;  31 756-759