BEYOND 18 F-FDG: INTRODUCTION TO NEW RADIOPHARMACEUTICALS

Transcription

1 BEYOND F-FDG: INTRODUCTION TO NEW RADIOPHARMACEUTICALS Asti Mattia Nuclear Medicine Department Santa Maria Nuova Hospital, Reggio Emilia, Italy

2 SUMMARY: F-Labelled Choline analogues. Comparison between F-FMCH and F-FECH in prostate cancer recurrence Correlation between F-FECH /CT and MR in Brain Cancer Brain Cancer: a radiopharmaceutical for every season 68 Ga-labelled Somatostatin analogues: 68 Ga-DOTATOC

3 F-LABELLED CHOLINE ANALOGUES Compounds where a -CH 3 group of the choline backbone was replaced with a F- labelled group. CH 3 CH 2 F F-FMCH HO N CH 3 Choline CH 3 CH 2 CH 2 F F-FECH Tumor cells usually exhibit an enhanced choline uptake due to the increased membrane phospholipids biosynthesis. Have the F-flourinated compounds the same behavior of choline? Is there a difference between F-FMCH and F-FECH?

4 F-LABELLED CHOLINE ANALOGUES From the literature: But conversely

5 COMPARISON BETWEEN F-FMCH AND F-FECH: Physiological distribution: Patient MBq 100 minutes post inj. 270 MBq 116 minutes post inj. F-FMCH F-FECH

6 COMPARISON BETWEEN F-FMCH AND F-FECH: Physiological distribution: Patient MBq 100 minutes post inj. 286 MBq 83 minutes post inj. F-FMCH F-FECH

7 COMPARISON BETWEEN F-FMCH AND F-FECH: Patient 3: assessment of a prostate tumor recurrence F-FMCH

8 COMPARISON BETWEEN F-FMCH AND F-FECH: Patient 4: assessment of a prostate tumor recurrence F-FECH

9 COMPARISON BETWEEN F-FMCH AND F-FECH: CONCLUSIONS: In our experience ( more than 50 patients were scanned with F-FMCH and more than 140 with F-FECH ) we did not found relevant differences in physiological or pathological distribution. Both radiopharmaceuticals can be successfully used for detecting prostate cancer recurrence and metastases Synthesis of F-FECH is easier and higher yielding respect to F-FMCH F-FMCH is commercially available

10 F-FECH IN BRAIN CANCER F-FECH also showed high effectiveness in the detection of Brain Cancer Clinical question 1: evaluation of tumor grading for projecting radioterapheutic plan RM /RM Different F-FECH uptake inside the lesion indicates different proliferation activity

11 F-FECH IN BRAIN CANCER Clinical question 2: Recurrence or necrosis after radiotherapy? RM / CT F-FECH uptake indicates recurrence Could the MR imaging, supported by spectroscopy, give sufficient information without using / CT scanning? Could the ratio between Choline and NAA peaks in MR spectroscopy be correlated with F-FECH uptake in?

12 CORRELATION BETWEEN F-FECH /CT AND MR Case 1: Disease or necrosis? RM / RM CHO CHO CR NAA Case 1: MR with spectroscopy would be sufficient to answer the question

13 CORRELATION BETWEEN F-FECH /CT AND MR Case 2: Recurrence or inflammation? RM Case 2: Using only MR with spectroscopy the result is uncertain ( inflammation ) F-FECH clearly shows no recurrence

14 CORRELATION BETWEEN F-FECH /CT AND MR Case 3: Recurrence or inflammation post surgery? RM / CT Case 3: using only MR with spectroscopy is not possible to give a sure answer ( maybe inflammation ) F-FECH / CT attests tumor recurrence

15 CORRELATION BETWEEN F-FECH /CT AND MR Case 4: Correlation between CHO/NAA signal in a multi-voxel spectroscopy and F-FECH SUV RM RM VS CHO / NAA F-FCH uptake (Bq/ml) Ch/NAA FCH - slice 2 CHO / vs F-FECH SUV R 2 = 0,84 Case 4: multi-voxel spectroscopy shows a good correlation with F-FECH SUV ( R 2 = 0.84 ) multi-voxel acquisition is not such accurate as single-voxel one 0 0,00 0,50 1,00 1,50 2,00 2,50 3,00 3,50 4,00 Ch/NAA

16 CORRELATION BETWEEN F-FECH /CT AND MR CONCLUSIONS: In many brain cancers, only MR imaging does not manage to give a certain answer to clinical questions such as discriminating inflammation, necrosis or tumor recurrence. The utilization of the single-voxel spectroscopy enhances the MR accuracy but the interpretation of some clinical cases remains doubtful. Multi-voxel spectroscopy data well correlate with F-FECH uptake However, single or multi-voxel acquisitions are time consuming and normally are performed in a few patients. In our experience the use of F-FECH / CT coupled with MR remains the best way for brain cancer detection and therapy assessment.

17 BRAIN TUMORS: A RADIOPHARMACEUTICAL FOR EVERY SEASON Left fronto-temporal lesion: MR indicates low grade glioma RM /CT [ F]-FET demonstrated a focal area of hypermetabolism ( SUVmax / BG = 4 ). F- FET / CT in association with MR showed a sensitivity and specificity of 93 % and 94 % respectively Courtesy of Dr. M. Farsad, Bolzano Hospital

18 BRAIN TUMORS: A RADIOPHARMACEUTICAL FOR EVERY SEASON RM FDG FLT Glioblastoma F-FLT more sensitive in the detection of high grade tumors Good correlation with Ki-67 proliferation index Better prognostic value Wei C et al. J Nucl Med 2005

19 BRAIN TUMORS: A RADIOPHARMACEUTICAL FOR EVERY SEASON F-DOPA: RM FDG DOPA The F-DOPA images reveal a clear-cut delineation of the tumor sites compared with F-FDG scans. The low uptake on F- FDG images most likely represents the lower grade associated with such tumors However the washout ratio would be related to the aggressiveness of the tumor

20 BRAIN TUMORS: A RADIOPHARMACEUTICAL FOR EVERY SEASON HYPOXIA MARKERS: RM /RM F-EF5 is a hypoxia marker of the same family of F-MISO and F-AZA Axial F-EF5 and fused /MR images show uptake of F-EF5 in anterior portion of tumor indicating intra-lesion hypoxia. Prof. Schubiger, University Hospital, Zurich

21 BRAIN TUMORS: A RADIOPHARMACEUTICAL FOR EVERY SEASON RECEPTORS EXPRESSION: 68 Ga-DOTATOC CT /CT 68 Ga-DOTATOC ( -TATE or -NOC ) are retained in tissues expressing somatostatin receptors Many tumors, above all neuroendocrine, breast, thyroid and brain, can express a high concentration of SSTR Gallium is a generator produced radionuclide with potentially many other applications in nuclear medicine.

22 BRAIN TUMORS: A RADIOPHARMACEUTICAL FOR EVERY SEASON CONCLUSIONS: Many radiopharmaceuticals, as well as F-FDG, are available for detecting brain cancers. Every radiopharmaceutical follows and attests a different metabolic pathway such as: AA transport and decarbossylation Cells proliferation and DNA synthesis Choline phosphorylation and cell membrane synthesis Receptors expression Tumor hypoxia The uptake of different radiopharmaceuticals could reflect a different stage of brain tumors further studies are needed.

23 68 GA-LABELLED SOMATOSTATIN ANALOGUES Case 1: metastases from breast cancer expressing SST receptors 68 Ga-DOTATOC / CT

24 68 GA-LABELLED SOMATOSTATIN ANALOGUES Case 2: bones metastases from breast cancer expressing SST receptors 68 Ga-DOTATOC / CT

25 68 GA-LABELLED SOMATOSTATIN ANALOGUES CONCLUSIONS: 68 Ga-DOTATOC and other somatostatin analogues are effective in the diagnosis of many tumors expressing SST receptors. 68-Gallium radionuclide is a generator produced radionuclide and so can be available also in centre without a cyclotron 68 Ga-DOTATOC / CT scans are the best way for assessing the effect of the therapy using 90 Y and 177 Lu-DOTATOC

26 ACKNOWLEDGEMENTS: Physicians: Dr. Roncalli M. Dr. Casali M. Dr.a Di Paolo M.L. Dr.a Filice A. Dr. Fraternali A. Dr. Versari A. Dr.a Salvo D. A PICTURE OF OUR DEPARTMENT Physicists: Dr. Sghedoni Dr.a Grassi E. Dr.a Fioroni F. Chemists: Dr. Iori M. Dr. Guidotti C. Dr.a Farioli D.