PET und PET/CT mit 18F-Fluorid in der Diagnostik von Knochenmetastasen

B. Schmiedel; H. Palmedo

doi:10.1055/s-2006-942260

Der Nuklearmediziner, Inhaltsverzeichnis

Der Nuklearmediziner 2006; 29(4): 255-264
DOI: 10.1055/s-2006-942260

Skelettszintigraphie - Update 2006

PET und PET/CT mit ¹⁸F-Fluorid in der Diagnostik von Knochenmetastasen

PET and PET/CT with ¹⁸F-Fluoride in the Diagnosis of Bone MetastasesB. Schmiedel¹ , H. Palmedo¹

¹Klinik und Poliklinik für Nuklearmedizin, Universitätsklinikum Bonn

Abstract

Zusammenfassung

Die Bestimmung des exakten Tumorstadiums im Rahmen der TNM-Klassifikation ist wichtig, um das optimale therapeutische Vorgehen für den Patienten festlegen zu können. Beim M-Staging ist es unabdingbar Knochenmetastasen nachzuweisen bzw. auszuschließen. Bei Tumoren wie dem Bronchialkarzinom, dem Prostata- und Mammakarzinom, bei denen häufig ossäre Metastasen zu beobachten sind, kommt der Knochenszintigraphie zum Metastasen-Screening eine entscheidende Rolle zu. Von dem Ergebnis der Knochenszintigraphie hängt z. B. ab, ob eine kurative Therapie möglich ist, ob eine operative oder chemotherapeutische Behandlung erfolgen muss. Die PET und PET/CT mit ¹⁸F-Natrium-Fluorid sind neue Untersuchungsmethoden zum Nachweis bzw. Ausschluss von ossären Metastasen. Die ¹⁸F-Fluorid-PET ermöglicht Schnittbilder mit hoher räumlicher Auflösung, die mit der Knochenszintigraphie nicht erreichbar ist. Die pharmakokinetischen Eigenschaften von ¹⁸F-Natrium-Fluorid sind günstig und führen zu einem hohen Tracer-Uptake im Knochen und einer schnellen Ausscheidung, was Aufnahmen hoher Qualität bereits eine Stunde p. i. ermöglicht. Im Vergleich zur planaren Ganzkörperszintigraphie kann die ¹⁸F-Fluorid-PET deutlich mehr Knochenmetastasen (vor allem in der Wirbelsäule) nachweisen. Im Vergleich zum Knochen-SPECT lassen sich deutlich weniger zusätzliche Metastasen nachweisen. Dies konnte insbesondere für das Bronchial- und Prostatakarzinom gezeigt werden. Bei einem kleinen Anteil der Patienten wird die ¹⁸F-Fluorid-PET trotz negativer Knochenszintigraphie einschl. SPECT Knochenmetastasen nachweisen können. Hingegen, lässt sich die Spezifität der SPECT durch die ¹⁸F-Fluorid-PET nicht merklich verbessern. Hier zeigt sich, dass neue Kamera-Systeme wie PET/CT und SPECT/CT aufgrund der CT-Komponente und der exakten anatomischen Lokalisierung der Mehranreicherung die Spezifität deutlich verbessern.

Abstract

The exact tumor stage needs to be determined with the help of the TNM classification before the optimal therapeutic procedure for the patient is proposed. If M-staging is under question bone metastases must be excluded or be proven. Bone scintigraphy plays a major role for bone metastases screening of patients with lung cancer, prostate and breast cancer in whom osseous disease is often present. The result of bone scintigraphy has a significant impact on further therapy e. g. whether curative treatment is possible, whether operative resection or chemotherapy must be performed. PET and PET/CT with ¹⁸F sodium fluoride are new imaging modalities for the detection of bone metastases. PET with ¹⁸F fluoride allows for cross sectional imaging with high resolution in a way that is not achievable by conventional bone scintigraphy. Pharmacokinetic properties of ¹⁸F fluoride are advantageous and lead to high tracer uptake and quick renal clearance. This allows the acquisition of high quality images as early as one hour after the injection. Compared with planar whole body scintigraphy, ¹⁸F fluoride is able to detect significantly more bone metastases (especially in the vertebral column). In comparison to bone SPECT, less additional metastatic lesions are detected by bone PET. This could be demonstrated in detail for lung and prostate cancers. In a small group of patients, ¹⁸F fluoride will diagnose osseous metastatic disease in spite of a negative planar whole body scintigraphy and a negative bone SPECT. However, specificity of bone SPECT is not markedly improved by ¹⁸F fluoride PET. It seems that new camera systems like PET/CT and SPECT/CT can enhance specificity impressively by adding the CT component to exactly localize a tracer accumulation.

Schlüsselwörter

PET - PET/CT - ¹⁸F Fluorid - Knochenmetastasen - Knochenszintigraphie

Key words

PET - PET/CT - ¹⁸F fluoride - bone metastases - bone scan - bone scintigraphy

Volltext

Referenzen

Literatur

1 Becker N, Wahrendorf J. Krebsatlas der Bundesrepublik Deutschland 1981-1990. Springer, Berlin 1998
2 Schalhorn A. Bronchialkarzinom: Möglichkeiten und Grenzen der Chemotherapie. Fortschr Med. 1985; 103 309-311
3 Schalhorn A. Bronchialkarzinom: Möglichkeiten und Grenzen der Chemotherapie. Fortschr Med. 1985; 103 453-456
4 Sobin L H, Wittekind C. TNM classification of malignant tumors. 5th ed. Wiley-Liss, New York 1997
5 Stahel R A, Ginsberg R, Havemann K. et al . Staging and prognostic factors in small cell lung cancer: a consensus report. Lung Cancer. 1989; 5 119-126
6 Stuschke M, Heilmann H P. Lunge und Mediastinum. In: Strahlentherapie. Scherer E, Sack H (Hrsg). Springer, Berlin 1996
7 Holmes E C. Surgical adjuvant therapy of NSCLC. J Surg Oncol. 1989; 42 (Suppl 1) 26-33
8 Dosoretz D, Galmarini D, Rubenstein J H. et al . Local control in medically inoperable lung cancer: analysis of its importance in outcome and factors determining the probability of tumor eradication. Int J Radiat Oncol Biol Phys. 1993; 27 507-516
9 Noordijk E M, van der Poest B, Hermans J, Wever A MJ, Leer J WH. Radiotherapy as an alternative to surgery in elderly patients with resectable lung cancer. Radiother Oncol. 1988; 13 83-89
10 Sandler H M, Curran W J, Turrisi A T. The influence of tumor size and pre-treatment staging on outcome following radiation therapy alone for stage I NSCLC. Int J Radiat Oncol Biol Phys. 1990; 10 9-13
11 Bülzebruck H, Danzer B, Hilkemeier G. et al . Metastasierung und Prognose des kleinzelligen Bronchialkarzinoms. Onkologe. 1998; 4 1039-1047
12 Line D, Deeley T J. The necropsy findings in carcinoma of the bronchus. Br J Dis Chest. 1971; 65 238
13 Wolf M. Kleinzelliges Bronchialkarzinom: Klinische Präsentation, Diagnostik und prognostische Faktoren. Onkologe. 1998; 4 1005-1018
14 Hansen H H, Muggia F M. Staging of inoperable patients with bronchogenic carcinoma with special reference to bone marrow and peritoneoscopy. Cancer. 1972; 30 1395-1401
15 Schalhorn A, Sunder-Plassmann L. Maligne Tumoren der Thorakal- und Mediastinalorgane. Internistische Onkologie. Wilmanns W, Huhn D, Wilms K (Hrsg). Thieme, Stuttgart 2000
16 Bonomi P D, Finkelstein D M, Ruckdeschel J C. et al . Combination chemotherapy vs. single agents followed by combinations chemotherapy in stage IV NSCLC: a study of the eastern cooperative oncology group. J Clin Oncol. 1989; 7 1602-1613
17 Drings P, Becker H, Bülzebruck H, Manke H G, Tessen H W. Chemotherapie des fortgeschrittenen nichtkleinzelligen Bronchialkarzinoms mit Ifosfamid und Etoposid. Tumordiagn Ther. 1990; 11 79-84
18 Spiegelman D, Maurer H, Ware J H. Prognostic factors in SCLC: an analysis of 1 521 patients. J Clin Oncol. 1989; 7 344-354
19 Rosell R, Lopez-Cabrerizo M P, Astudillo J. Preoperative chemotherapy for stage III A NSCLC. Curr Opin Oncol. 1997; 9 149-155
20 Albain K S, Crowley J J, Leblanc M, Livingston R B. Determinants of improved outcome in SCLC: an analysis of the 2 580 patients southwest oncology group data base. J Clin Oncol. 1990; 8 1563-1574
21 Manegold C, Bülzebruck H, Drings P, Vogt-Moykopf I. Prognostische Faktoren beim kleinzelligen Bronchialkarzinom. Onkologe. 1989; 12 240-245
22 Golz R, Störkel S. Anatomie und Pathologie des Prostatakarzinom. In: Prostatakarzinom. Hinkelbein W, Miller K, Wiegel T (Hrsg). Springer, Berlin 1999
23 Statistisches Bundesamt .Gesundtheitswesen. Fachserie 12, Reihe 4. Todesursachen in Deutschland. Wiesbaden 1994
24 Saitoh H, Hida M, Shimbo T. et al . Metastatic patterns of prostatic cancer. Cancer. 1984; 54 3078-3084
25 De la Monte S M, Moore G W, Hutchins G M. Metastatic behaviour of prostate cancer. Cancer. 1986; 58 985-993
26 Ravery V, Schmid H P, Toublanc M, Boccon-Gibod L. Is the percentage of cancer in biopsy cores predictive of extracapsular disease in T1-T2 prostate cancer?. Cancer. 1996; 78 1079-1084
27 Badalament R A, Miller M C, Peller P A. et al . An algorithm for predicting nonorgan confined prostate cancer using the results obtained from sexant core biopsies with prostate specific antigen level. J Urol. 1996; 156 1375-1380
28 Breul J. et al .Fehler bei der präoperativen Bestimmung des lokalen Tumorstadiums bei der radikalen Prostatektomie. In: Hartung U, Kropp J (Hrsg). Urologische Beckenchirurgie. Springer, Berlin 1991
29 Rorvik J, Halvorsen O J, Servoll E, Haukaas S. Transrectal ultrasonography to assess local extent of prostatic cancer before radical prostatectomy. Br J Urol. 1994; 73 65-69
30 Partin A. et al . PSA in the staging of localized prostate cancer: influence of tumor differentiation tumor volume and benigne hyperplasia. J Urol. 1990; 143 747
31 Kleer E, Oesterlin J E. PSA and staging of localized prostate cancer. Urol Clin North Am. 1993; 20 695-705
32 Catalona W J, Smith D S, Ratliff T L, Basler J W. et al . Measurement of PSA in serum as a screening test for prostate cancer. N Engl J Med. 1991; 324 1156-1161
33 Wirth M P, Frohmüller H GW. PSA and prostate acid phosphatase in the detection of early prostate cancer and the prediction of regional lymph node metastases. Eur Urol. 1992; 22 27-32
34 Shreve P D, Grossman H B, Gross M D, Wahl R L. Metastatic prostate cancer: initial findings of PET with F-18 fluoro-D-glucose. Radiology. 1996; 199 751-756
35 Partin A W, Kattan M W, Subong E N. et al . Combination of PSA, clinical stage, and Gleason Score to predict pathological stage of localized prostate cancer. JAMA. 1997; 277 1445-1451
36 Klän R, Meier T, Knispel H H, Wegner H E, Miller K. Laparoscopic pelvic lymphadenectomy in prostatic cancer. Urol Int. 1995; 55 78-83
37 Catalona W J, Smith D J. 5-year tumor recurrence rates after anatomical radical retropubic prostatectomy for prostate cancer. J Urol. 1994; 152 1837-1842
38 Ohori M, Goag J R, Wheeler T M. et al . Can radical prostatectomy alter the progression of poorly differentiated prostate cancer?. J Urol. 1994; 152 1843-1849
39 Hanks G E, Lee W R, Haulon M S. et al . Conformal technique dose escalation for prostate cancer. Int J RadiatOncol Biol Phys. 1996; 35 861-868
40 Zietman A L, Shipley W U. Randomized trials in loco-regionally confined prostate cancer: past present and future. Semin Radiat Oncol. 1993; 3 210-220
41 Epstein J. et al . Correlation of pathologic findings with progression after radical retropubic prostatectomy. Cancer. 1993; 71 3586
42 Perez C A, Hanks G E, Leibel S A. et al . Localized carcinoma of the prostate (stages T1, T2 and T3). Cancer. 1993; 72 3156-3173
43 Chybowski F M, Keller J L, Bergstrahl E J, Oesterling J E. Predicting radionuclide bone scan finding in patients with newly diagnosed untreated prostate cancer. J Urol. 1991; 145 313-318
44 Andriole G L, Kavoussi L R, Torrence J R. Transrectal ultrasonography in the diagnosis and staging of the carcinoma of the prostate. J Urol. 1988; 140 758-760
45 Noldus J, Stamey T A. Limitations of serum PSA in predicting peripheral and transition zone cancer volumes as measured by correlation coefficients. J Urol. 1996; 155 232-237
46 Kelsey J L, Gammon M D. The epidemiology of breast cancer. Cancer. 1991; 41 146-165
47 Berg J W, Hutter R V. Breast cancer. Cancer. 1995; 75 257-269
48 Sondik E J. Breast cancer trends. Incidence, mortality and survival. Cancer. 1994; 74 995-999
49 Possinger K, Große Y. Mammakarzinome und gynäkologische Tumoren. Internistische Onkologie. Wilmanns W, Huhn D, Wilms K (Hrsg). Thieme, Stuttgart 2000
50 Spratt J S, Donegan W L. Cancer of the breast. Saunders, Philadelphia 1979
51 Tabar L, Grad A, Holmberg L H. et al . Reduction in mortality from breast cancer after mass screening with mammography. Lancet. 1985; 1 829
52 Boag J W, Jaybittle J L, Fowler J R. The number of patinets required in a clinical trial. Brit J Radiol. 1971; 44 122
53 Smart C R, Myers M H, Gloeckler L A. Implications from SEER data on breast cancer management. Cancer. 1978; 41 787
54 Koscielny S M, Tubiana M, Le M G. et al . Breast cancer. Relationship between the size of the primary tumor and the probability of metastatic dissemination. Brit J Cancer. 1984; 49 709
55 Donegan W L. Epidemiology. In: Donegan WL, Spratt JS. Cancer of the breast. Saunders, Philadelphia 1979
56 Foster Jr R S, Lang S P, Constanza M C. et al . Breast self-examination practices and breast cancer stage. New Engl J Med. 1978; 299 265
57 Andersson I. Mammographic screening and mortality from breast cancer: Malmö mammographic screening trial. Brit J Med. 1988; 297 943-948
58 Frisell J, Eklund G, Hellström L. et al . Randomized study of mammography screening - preliminary report on mortality in the Stockholm trial. Breast cancer research and treatment. 1991; 18 49-56
59 Miller A B, Baines C J, To T. et al . Canada national breast screening study. Can Med Assoc J. 1992; 147 1459-1488
60 Meuret G. Grundlagen des Mammakarzinoms. In: Mammakarzinom. Meuret G (Hrsg). Thieme, Stuttgart 1995
61 Clark G M, Sledge G W, Osborne C K, McGuire W L. Survival from first recurrence: relative importance of prognostic factors in 1 015 breast cancer patients. J Clin Oncol. 1987; 5 55-61
62 Come S E, Schnipper L E. Myelophtisisanemia and other aspects of bone marrow involvement. In: Harris JR, Hellman S, Henderson IC, Kinne DW. Breast diseases. Lippincott, Philadelphia 1991; 761-766
63 Perez D J, Powles T J, Milan J. et al . Detection of breast carcinoma metastases in bone: relative merits of x-rays and skeletal scintigraphy. Lancet. 1983; 2 613-616
64 Rossing N, Munck O, Nielsen S P. et al . What do early bone scans tell about breast cancer patients?. Eur J Cancer Clin Oncol. 1982; 18 629-636
65 Kamby C, Bruun Rasmussen B, Kristensen B. Prognostic indicators of metastatic bone disease in human breast cancer. Cancer. 1991; 68 2045-2050
66 Muss H B. Endocrine therapy for advanced breast cancer: a review. Breast cancer Res Treat. 1992; 21 15-26
67 Diel I J, Solomayer E F, Costa S D. et al . Reduction in new metastases in breast cancer with adjuvant clodronate treatment. N Engl J Med. 1998; 339 357-363
68 Conte N, Giannessi P G, Latreille J. et al . Delayed progression of bone metastaseswithb pamidronate therapy in breast cancer patients: a randomized, multicenter phase III trial. Br J Cancer. 1994; 70 554-558
69 Van Holten-Verzantvoort A TM, Hermans J. et al . Does supportive pamodronate treatment prevent or delay the first manifestation of bone metastases in breast cancer patients?. Eur J Cancer. 1996; 32 450-454
70 Aberzik W J, Silver B, Henderson I C. et al . The use of radiotherapy for treatment of isolated locoregional recurrence of breast carcinoma after mastectomy. Cancer. 1986; 58 1214
71 Janjan N A, McNeese M D, Buzdar A U. et al . Management of locoregional recurrent breast cancer. Cancer. 1986; 58 1552
72 Noguchi S, Miyauchi K, Nishizawa Y. et al . Results of surgical treatment for sternal metastases in breast cancer. Cancer. 1987; 60 2524-2531
73 Schirrmeister H. et al . Early detection and accurate description of extent of metastatic bone disease in breast cancer with fluoride ion and positron emission tomography. J Clin Oncol. 1999; 17 2381
74 Gambhir S S, Czernin J, Schwimmer J. et al . A tabulated summary of the FDG-PET literature. J Nucl Med. 2001; 42 1S-93S
75 Blau M, Nagler W, Bender M A. A new isotope for bone scanning. J Nucl Med. 1962; 3 332-334
76 Cook G, Fogelman I. The role of positron emission tomography in skeletal disease. Seminars in Nuclear Medicine. 2001; 1 50-61
77 Hawkins R A, Choi Y, Huang S C. et al . Evaluation of the skeletal kinetics of fluorine-18-fluoride ion with PET. J Nucl Med. 1992; 33 633-642
78 Hoh C K, Hawkins R A, Dahlbom M. et al . Whole body skeletal imaging with F-18 fluoride ion and PET. J Comp Assist Tomogr. 1993; 17 34-41
79 McNeil B J. et al . Fluroine-18 bone scintigraphy in children with osteosarcoma or Ewing's sarcoma. Radiology. 1973; 109 627-631
80 Buck A C. et al . Serial Fluorine-18 bone scans in the follow-up of carcinoma of the prostate. Br J Urol. 1975; 47 287-294
81 Rosenfield N, Treves S. Osseous and extraosseousuptake of fluorine-18 and techentium-99m polyphosphate in children with neuroblastoma. Radiology. 1974; 111 127-133
82 Schirrmeister H, Rentschler M, Kotzerke J. et al . Skeletal imaging with F-18 NaF PET and comparison with planar scintigraphy. Fortschr Röntgenstr. 1998; 168 451-456
83 Schirrmeister H, Guhlmann C A, Diederichs C G, Träger H, Reske S N. Planar bone imaging vs. F-18 PET in patients with cancer of the prostate, thyroid and lung. J Nucl Med. 1999; 40 1623-1629
84 Schirrmeister H, Glatting G, Hetzel J, Nussle K, Arslandemir C, Buck A K, Dziuk K, Gabelmann A, Reske S N, Hetzel M. Prospective evaluation of the clinical value of planar bone scans, SPECT, and (18)F-labeled NaF PET in newly diagnosed lung cancer. J Nucl Med. 2001; 42 1800-1804
85 Palmedo H, Schaible R, Textor J, Ko Y, Grohé C, Mallek D von, Ezziddin S, Reinhardt M J, Biersack H J. PET with ¹⁸F Fluoride compared to bone scintigraphy in the diagnosis of bone metastases: results of a prospective study. J Nucl Med. 2002; (Suppl) 1150
86 Lonneux M, Borbath I I, Berliere M, Kirkove C, Pauwels S. The Place of Whole-Body PET FDG for the Diagnosis of Distant Recurrence of Breast Cancer. Clin Positron Imaging. 2000; 3 45-49
87 Ohta M, Tokuda Y, Suzuki Y, Kubota M, Makuuchi H, Tajima T, Nasu S, Suzuki Y, Yasuda S, Shohtsu A. Whole body PET for the evaluation of bony metastases in patients with breast cancer: comparison with ⁹⁹Tcm-MDP bone scintigraphy. Nucl Med Commun. 2001; 2 875-879
88 Yang S N, Liang J A, Lin F J, Kao C H, Lin C C, Lee C C. Comparing whole body ⁽¹⁸⁾F-2-deoxyglucose positron emission tomography and technetium-99m methylene diphosphonate bone scan to detect bone metastases in patients with breast cancer. J Cancer Res Clin Oncol. 2002; 128 325-328
89 Marom E M, McAdams H P, Erasmus J J, Goodman P C, Culhane D K, Coleman R E, Herndon J E, Patz Jr E F. Staging non-small cell lung cancer with whole-body PET. Radiology. 1999; 212 803-809
90 Garcia J R, Simo M, Perez G, Soler M, Lopez S, Setoain X, Lomena F. ^99mTc-MDP bone scintigraphy and ¹⁸F-FDG positron emission tomography in lung and prostate cancer patients: different affinity between lytic and sclerotic bone metastases. Eur J Nucl Med Mol Imaging. 2003; 30 1714
91 Even-Sapir E, Metser U, Mishani E, Lievshitz G, Lerman H, Leibovitch I. The Detection of Bone Metastases in Patients with High-Risk Prostate Cancer: ^99mTc-MDP Planar Bone Scintigraphy, Single- and Multi-Field-of-View SPECT, ¹⁸F-Fluoride PET, and ¹⁸F-Fluoride PET/CT. J Nucl Med. 2006; 47 287-297
92 Buscombe J R, Holloway B, Roche N, Bombardieri E. Position of nuclear medicine modalities in the diagnostic work-up of breast cancer. Q J Nucl Med Mol Imaging. 2004; 48 109-118
93 Ghanem N, Altehoefer C, Kelly T, Lohrmann C, Winterer J, Schafer O, Bley T A, Moser E, Langer M. Whole-body MRI in comparison to skeletal scintigraphy in detection of skeletal metastases in patients with solid tumors. In Vivo. 2006; 20 173-182
94 Frat A, Agildere M, Gencoglu A, Cakir B, Akin O, Akcali Z, Aktas A. Value of whole-body turbo short tau inversion recovery magnetic resonance imaging with panoramic table for detecting bone metastases: comparison with ^99mTc-methylene diphosphonate scintigraphy. J Comput Assist Tomogr. 2006; 30 151-156

Prof. Dr. H. Palmedo

Klinik und Poliklinik für Nuklearmedizin · Universitätsklinikum Bonn

Sigmund-Freud-Str. 25

53105 Bonn

eMail: holger.palmedo@ukb.uni-bonn.de