MULTİPL MYELOMA VE AMİLOİDOZİSTE NÜKLEER TIP

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1 MULTİPL MYELOMA VE AMİLOİDOZİSTE NÜKLEER TIP Prof.Dr.Emel ÖZTÜRK Ufuk Üniversitesi Tıp Fakültesi Nükleer Tıp A.D.

2 Multipl Myeloma Aktif Hastalık ile MGUS/Sinsi Ayrımı Evreleme Organ tutulumunun değerlendirilmesi Prognoz belirleme Tedavi Yanıtını saptama Yeniden evreleme 2

3 Multipl Myeloma Morfolojik/Fonksiyonel Görüntüleme BEKLENTİLER: Osteoporoz tanısı Osteolitik Lezyonların varlığı ve yaygınlığı Kemik iliği infiltrasyonunun gösterilmesi Kemik dışı yumuşak doku lezyonlarının gösterilmesi Prognozu yansıtabilmesi Tedavi yanıtını yansıtması 3

4 Multipl Myeloma-Kemik Sintigrafisi Kemik Lezyonları: Saf osteolitik,osteoblastik yanıt yok 4

5 Multipl Myeloma-Kemik Sintigrafisi Duyarlılık:%75, Lezyon Saptama:%10 Clin Nucl Med ;30:

6 Multipl Myeloma - FDG PET Aktif Hastalık-MGUS/Sinsi Hastalık Ayrımı 6

7 Multipl Myeloma - FDG PET Aktif Hastalık-MGUS/Sinsi Hastalık Ayrımı Görüntüleri Paylaşan Prof.Dr.Ayşe Mudun a teşekkürler. 7

8 Multipl Myeloma Evreleme Evre I ISS Serum 2 mikrogl.: <3.5 mg/l Serum Albumin : 3.5 g/dl DURIE/SALMON Hb:>10 mg/dl, Serum Ca:N veya <10.5 mg/dl Direk Film: N veya soliter Lezyon Düşük M-Komponent üretimi: IgG:<5.0 g/dl IgA :<3.0 g/dl Bence-Jones Protein: <4 g/24 saat Evre II Evre I ve II ye uymayan Evre I ve II ye uymayan Evre III Serum 2 mikrogl.: 5.5mg/L Hb:<8.5 mg/dl, Serum Ca:>12 mg/dl Direk Film: İleri litik lezyonlar Yüksek M-Komponent üretimi: IgG:>7 g/dl IgA : >5 g/dl Bence-Jones Protein: >12 g/24 saat 8

9 Multipl Myeloma Evreleme Direk Röntgen Filmi Osteoporoz Osteolitik Lezyonlar 9

10 Multipl Myeloma Evreleme Direk Röntgen Filmi Yanlış negatif : %30-70 Yorum birey bağımlı Lezyon saptama için kemik mineral kayıp : %30-50 Aktif hastalık-mgus/sinsi hastalık ayrımı yapamaz Kemik İliği infiltrasyonunu göstermez Ekstramedüller lezyonlar saptanamaz Osteoporoz ayırıcı tanısı yetersiz 10

11 Multipl Myeloma Evreleme BT AVANTAJ Kemik Destrüksiyonu Ekstramedüller lezyonlar Osteoporoz DEZAVANTAJ Osteopeni Kemik iliği İnfiltrasyonu Radyasyon Dozu Yüksek 11

12 Multipl Myeloma Evreleme MR K.İ. infiltrasyonu saptanır Aksiyel iskelet için iyi Tarama zamanı uzun Kranium, kot,klavikula değerlendirmede yetersiz Tüm Vücut MR 12

13 Multipl Myeloma Evreleme PET Fokal + Diffüz Fokal + Diffüz+Ekstramedüller Diffüz 13

14 Multipl Myeloma Evreleme PET 14

15 Multipl Myeloma Evreleme PET 15

16 Multipl Myeloma Evreleme FDG/PET Aktif (İskelet,Ekstramedüller) hastalık saptanır Genellikle evreyi yükseltir Fokal lezyon dedeksiyonunda Tc-99m MIBI ile MR dan üstün Kot lezyonlarını saptamakta MR dan üstün Vertebradaki infiltrasyon için MR üstün 16

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18 Multipl Myeloma-D/S PLUS Evreleme Kriterleri Sınıflandırma MGUS Evre IA Evre IB Evre II A/B Evre III A/B Tüm Vücut MR ve/veya FDG-PET Hepsi Negatif Normal iskelet sistemi veya soliter lezyon (Smoldering) <5 fokal lezyonlar veya hafif diffüz hastalık 5-20 fokal lezyonlar veya orta diffüz hastalık >20 fokal lezyonlar veya ciddi diffüz hastalık 18

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20 Multipl Myeloma-Tedavi Yanıtı 20

21 Multipl Myeloma-Tedavi Yanıtı 21

22 Multipl Myeloma Tedavi Yanıtı Tedavi yanıt Tedavi Öncesi 22

23 Multipl Myeloma Tedavi Yanıtı Tedavi yanıt Tedavi Sonrası 23

24 Multipl Myeloma Tedavi Yanıtı Tedavi yanıt KİT sonrası 3.ay 24

25 Multipl Myeloma Tedavi Yanıtı Tedavi yanıt KT sonrası 3.ay 25

26 Multipl Myeloma FDG/PET Prognoz Tayini Tedavi yanıt Purpose: We assessed the prognostic value of F-18 fluorodeoxyglucose (FDG) uptake in the bone marrow of patients with multiple myeloma (MM) in comparison with Tc-99m methoxy-isobutyl-isonitrile (MIBI). Methods: The extent and intensity of FDG and MIBI uptake in the bone marrow of 18 patients with a recent diagnosis of MM were assessed by visual score and by calculating the mean SUV (msuv) for FDG and the femora/ thigh ratio (TG/BKG, Target/Background ratio) for MIBI images. These parameters were correlated with clinical indexes of disease using hemoglobin and beta-2-microglobulin levels and plasma cell infiltrate (PCI) percentage. The mean values of the visual score, msuv, and TG/BKG levels were compared in patients deceased after a relatively short follow-up (n 9; group A) and in patients with a longer survival or were alive at the end of the study (n 9; group B). Results: Significant correlations of msuv and TG/BKG values with PCI percentages and beta-2-microglobulin were found (P 0.05). The extent of FDG and MIBI bone marrow uptake was greater in patients of group A (P 0.01). Higher values of msuv (P 0.01) and TG/BKG (P 0.05) were also observed in patients of group A. These results were consistent with the differences (not statistically significant) in hemoglobin, albumin, beta-2-microglobulin levels, and PCI percentages observed in the 2 groups. Conclusion: Our study demonstrates that an increase of FDG bone marrow uptake may predict a more aggressive disease, as much as MIBI uptake. Therefore, an additional analysis of FDG bone marrow images should be performed in patients undergoing PET studies during the initial staging of MM. (Clin Nucl Med 2010;35: 1 5) 26

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28 28 ort.takip:66.8 ay ort.takip:19.2 ay

29 Multipl Myeloma Tc-99m MIBI Tedavi yanıt 29

30 Multipl Myeloma Tc-99m MIBI Tedavi yanıt NORMAL DİFFÜZ FOKAL 30

31 Multipl Myeloma Tc-99m MIBI Tedavi yanıt MGUS Aktif Myelom 31

32 Multipl Myeloma Tc-99m MIBI Evreleme Tedavi yanıt Br J Haematol. 2007;136: We evaluated the additional benefit of Technetium99-sestamibi (99mTc-MIBI) scanning in comparison with standard X-ray techniques for multiple myeloma patients either at diagnosis or during follow-up. Between February 2001 and January 2005, 397 whole body scans were acquired. On 229 scans performed at diagnosis, 146 (64%) were positive and 81 cases have discordant X-ray results. The sensitivity of 99mTc-MIBI and X-ray were 77% and 45% respectively. As a result of 99mTc-MIBI, 40% of asymptomatic myeloma patients were up-staged. The positivity of 99mTc- MIBI correlated significantly with all of the most relevant clinical and biological parameters. Multivariate analysis selected only high reactive C protein (P ¼ 0Æ0005), bone marrow infiltration (P ¼ 0Æ02) and bone pain (P ¼ 0Æ002) as factors affecting 99mTc-MIBI pattern. In 22 patients with solitary myeloma, 99mTc-MIBI was positive in 86% of cases and detected more disease sites than X-ray. Among 168 scans performed during follow-up, 99mTc-MIBI presented high specificity in patients showing a complete response (CR; 86%), and correlated with myeloma activity and with response to therapy. At multivariate analysis, a positive pattern correlated with bone marrow infiltration (P ¼ 0Æ002) and disease status other than CR (P ¼ 0Æ03). We conclude that 99mTc- MIBI scanning is an additional diagnostic tool with a high specificity for the staging and the follow-up of multiple myeloma patients. 32

33 Multipl Myeloma Tc-99m MIBI Tedavi yanıt Staging and therapy monitoring of multiple myeloma by 99mTc-sestamibi scintigraphy: a five year single center experience. J Exp Clin Cancer Res. 2005: 24: The aim of the present study was the evaluation of the diagnostic value of 99mTc sestamibi (MIBI) in the detection of bone marrow involvement in patients suffering from multiple myeloma (MM) and its possible role in the follow up. Between 1998 and 2003, 68 patients with MM and 42 pts with monoclonal gammopathy of undetermined significance (MGUS) were consecutively enrolled in this study. 51/68 MM patients had active disease (AD), 11/62 were in complete remission (CR) and 6/68 in partial remission (PR) after chemotherapy. 18 patients with MM repeated a 99mTc MIBI scintigraphic study at least 2 months after high dose chemotherapy. All the scans were scored semi quantitatively according to extension and intensity of tracer uptake. All MGUS pts had a negative 99mTc MIBI. As far as the MM pts are concerned, 54/68 (49%) pts (48 with AD, 5 with PR and 1 with CR) had a positive 99mTc MIBI scan, while the 99mTc MIBI scan was negative in 14/68 pts (10 with CR, 1 with PR and 3 with AD). The overall sensitivity of the 99mTc MIBI scintigraphy was 92%; specificity was 96%. In the follow up of the pts treated with chemotherapy 99mTc MIBI closely paralleled the activity of myeloma bone disease. In conclusion, these results indicate that 99mTc MIBI scintigraphy closely reflects myeloma disease activity in the bone marrow, and that a negative 99mTc MIBI scan in patients with suspected MM clearly, though not absolutely, indicates absence of disease or clinical remission. The results of this study suggest a clear diagnostic value of 99mTc MIBI scintigraphy in patients with MM and its potential role during the follow up for the monitoring of MM bone disease. 33

34 Multipl Myeloma Tc-99m MIBI Tedavi yanıt Tedavi Öncesi Tedavi Sonrası 34

35 Multipl Myeloma Tc-99m MIBI Prognoz Tayini Tedavi yanıt Clin Nucl Med 2010;35:

36 Multipl Myeloma Yöntemler Direk R BT ÇKBT MR PET/BT MIBI Maliyet Radyasyon Dozu Çekim Zamanı Duyarlılık +/ Mevcudiyet Uzaysal Rezolüsyon Erken Tanı K.İ / Osteolitik Lezyon +/ MM Aktivite Tayini Tedavi Yanıtı / Subcm.Lezyon +/ MGUS/MM Ayrımı Fokal Lezyonlar /++ Diffüz Lezyonlar

37 Amiloidozis Kemik Sintigrafisi Tedavi yanıt 37

38 Amiloidozis Tc-99m Aprotinin Tedavi yanıt J Nucl Med 2003: 44;

39 Amiloidozis Tc-99m Aprotinin Tedavi yanıt Kardiyak İntestinal Eller Dil Submandibuler bez J Nucl Med 2003: 44;

40 Amiloidozis I-123 SAP Tedavi yanıt (Serum Amiloid P Komponent) Dalak Sürrenal N Engl J Med ;: