Short summary of published results of PET with fluoromethylcholine (18F) in prostate cancer

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1 Short summary of published results of PET with fluoromethylcholine (18F) in prostate cancer JN TALBOT and all the team of Service de Médecine Nucléaire Hôpital Tenon et Université Pierre et Marie Curie, Paris, France

2 PET or PET/CT and prostate cancer In France, the most frequent cancer in man after 50 Potential indications of PET or PET/CT Assessment :. Biopsy guidance of a primary lesion, in particular when PSA serum levels are high and random multiple biopsies negative. Initial staging : LN and distant metastases (bone ) Therapy evaluation (surgery, radiotherapy, brachytherapy, thermotherapy, hormone therapy ) : search for residual disease Recurrence. Restaging of a demonstrated or highly suspicious recurrence. Localisation of biologic recurrences (rising PSA serum levels) : 40% of patients after radical treatment

3 FDG PET and prostate cancer Of little help in non-aggressive prostate cancer : - Glucose metabolism is not clearly enhanced High concentration in urine hampers pelvic images of a good quality Performances < bone scintigraphy for the detection of mets Yeh, Nucl Med Biol 1996 Schreve, Radiology Low sensitivity and low specificity (prostatitis or benign hypertrophy can be FDG +) for the detection of primary lesions Low sensitivity for LN or distant metastases Poor results in the detection of recurrences : 30 % accuracy Seltzer, J Urol 1999 Non-recommended indication (at least in Europe) except for aggressive forms of prostate cancer

4 CHOLINE (11C) AND FLUORINATED CHOLINE ANALOGUES Tracers of the lipid metabolism showed better performance in prostate cancer MR spectroscopy reveals high amounts of choline in prostate cancer Choline (11C) is thus a good candidate for molecular imaging of prostate cancer 11C poses many logistical problems Fluorinated (18F) choline analogues, easier to deliver: fluoromethylcholine-(18f) or FCH with normal n biodistribution similar to choline (11C) + urinary excretion

5 FCH PET/CT evaluation of the prostate bed and the pelvis Cancer uptake occurs as early as 1st minute Urinary tract excretion at 4th minute perform early dynamic acquisitions (Price, J. Urology, 2002) Sutinen, EJNM 2004 prostate cancer

6 FCH PET/CT usual IMAGING PROTOCOL FCH injection 4 MBq / kg TDM + FCH Dynamic Acquisition Prostatectomie / RT + Curage Whole body acquisition 8 x 1 min frames on pelvis = 8 min 10 bed posisitions of 3 minutes

7 FCH IN SEARCH FOR A PRIMARY LESION Short series and somewhat discrepant results Schmid, Radiology 2006: 8 pts, Standard of truth : prostatectomy concordance 1/8, probable FP results 2/8 Kwee, JNM 2006: 15 pts, better specificity by adding late images (dual time) Kwee, Mol Imaging 2008: 15 pts, 90 sextants SUVmax. Standard of truth : prostatectomy In 13 patients, the sextant with the highest SUVmax corresponded to the largest malignant tumour in the specimen, but sextants with small malignant volume can be negative Igerc, EJNMMI 2008 :. 20 patients, identification of neoplastic lesions in 5, no help of dual time In this setting FCH is still in evaluation (check the most active e lesion?) and requesting comparison with diffusion MRI...

8 FCH in SEARCH FOR A PRIMARY LESION Hôpital Tenon

9 INITIAL STAGING with FCH T staging : main drawbacks are the limited spatial resolution of PET and of the non-specific FCH uptake by non-malignant prostate tissue. FCH PET/CT has been proposed to increase radiotherapy on dominant areas (Kwee JNM 2006). N staging: (Hacker J.Urol 2006, Husarik EJNMMI 2008) Lymph node dissection should include the FCH+ nodes But there are false negative results (13/15 patient based) due to small metastases (and Se declines when sentinel node detection and histology is used as standard of truth) Distant LN metastases can be detected much more effectively than with CT alone, but beware of non-specific uptake in reactive LN (namely inguinal LN)

10 Initial staging with FCH: juxta-rectal lymph nodes (confirmed) Post injection Delayed «whole body»

11 INITIAL STAGING with FCH. Illustration FCH PET CT 73 yo pt, bilateral prostate ADK Gleason 6 (3+3), PSA 8 ng/ml Bone scintigraphy : M+ or Paget s disease? Radiotherapy or hormone therapy? FCH + bone metastasis that was further confirmed

12 INITIAL STAGING, same situation in another pt FCH PET Paget s disease was confirmed FCH PET/CT fusion

13 INITIAL STAGING with FCH M staging and restaging : (Beheshti Eur J Nucl Med Mol Imaging 2008) - Detection of unexpected bone metastases Bone involvement (one single focus on bone scintigraphy or fluoride-(18f) PET/CT)

14 FCH Fluoride Fig. 3 18F FCH positive (a) and 18F fluoride-negative (b) bone marrow metastases (black arrow) of t M.Beheshti, et al. Eur J Nucl Med Mol Imaging (2008) 35: he thoracic spine without morphological CT changes (white arrow). Lesion was finally confirmed by follow-up; no hormone therapy. M.Beheshti, et al. Eur J Nucl Med Mol Imaging (2008) 35:

15 FCH Fluoride Fig. 4 18F FCH negative (a) and 18F fluoride PET CT positive (b) lesion (arrow) in a malignant sclerotic lesion (HU 880) of the lumbar spine (L1). Lesion was finally confirmed by follow-up; patient was under hormone therapy. M.Beheshti, et al. Eur J Nucl Med Mol Imaging (2008) 35:

16 Results of Beheshti Eur J Nucl Med Mol Imaging 2008, detection of bone mets at staging or restaging Lesion based FCH F Na Sensitivity 74% 81% Specificity 99% 93% Accuracy 85% 86%

17 FCH for RECURRENCE DETECTION Schmid, Radiology /9 FCH + (PSA = 14 ± 15 ng/ml) Local recurrence = 4, LN mets = 5, Bone mets = 1 Heinisch, Mol Imaging Biol /17 FCH + = 47% (PSA < 5 ng / ml) Cimitan, EJNMMI /100 FCH + = 54% (PSA < 5 ng / ml) FCH cases : 89% PSA < 4, 87% initial Gleason s score <8 Husarik, EJNMMI /68 FCH + = 84% and 71% when PSA < 2 ng/ml. Pelosi, Radiol Med /56 FCH + = 43% and 20% for PSA < 1 ng/ml, 44% 1<PSA<5 Steinert, Nuklearmedizin phase FCH PET/CT : 38/47 FCH + = 81%, and 31% for PSA < 2 ng/ml. Late acquisition contributed to assessment in 10/47= 21% Wang, Radiother oncol FCH guidance of re-irradiation of local recurrence resulted in a larger GTV

18 LOCAL RECURRENCE. Illustration with FCH PET/CT prostate adenocarcinoma, initial Gleason 8 External radiotherapy in 1996 Biologic recurrence : PSA 25 ng/ml Médecine nucléaire Hôpital Tenon

19 LYMPH NODE RECURRENCE. Illustration with FCH PET/CT 49 yo ADK prostate Gleason 8 Enantone External radiotherapy in 2000 Biologic recurrence PSA 30 ng/ml FDG MRI Médecine nucléaire Hôpital Tenon

20 BONE RECURRENCE. Illustration with FCH PET/CT Prostatectomy in 1998 Biologic recurrence PSA 9 ng/ml Negative bone scintigraphy Zoladex treatment Médecine nucléaire Hôpital Tenon

21 OCCULT RECURRENCE 69 yo pt 2003: radical prostatectomy, Gleason : PSA 2.5 ng/ml Negative abdomino-pelvic CT and bone scintigraphy LN histology : recurrence Service de Médecine Nucléaire, Hôpital Tenon

22 RESTAGING with FCH : one recurrent thoracic LN confirmed FDG FCH Service de Médecine Nucléaire, Hôpital Tenon

23 Cervical FCH-(18F) PET/CT Diagnosis of autoimmune thyroiditis was confirmed Message: FCH may be FP in inflammation Service de Médecine Nucléaire, Hôpital Tenon

24 FREQUENCE OF FCH + PET/CT ACCORDING TO PSA SERUM LEVELS 100% Experience of Hôpital Tenon 80% 78.5 % 60% 40% 20% 11 % 0% <1 1 _ 2 2 _ 5 5 _ 10 10_20 > 20 NEGATIVE PET POSITIVE PET

25 140 Detection rate of FCH PET/CT (n=305) POS NEG 70 0 < 1 <1.5 < 2 < 3 < 4 >/=4 PSA ng/ml Current experience of Dr M Cimitan, Aviano (Italy)

26 INFLUENCE OF THE SLOPE OF PSA INCREASE? Our experience in 46 patients: FCH + : Higher PSA serum concentration 7.6 vs. 2.0 ng/ml (p<0.05) Higher PSA velocity 6.0 vs. 1.5 ng/ml/year (p<0.05) PSA SERUM CONCENTRATION < 5ng/mL: 1/11=9% FCH + when velocity < 1.2 ng/ml/year 8/12=67% FCH + when velocity > 1.2 ng/ml/year Choline (11C) : OP080 by Giovacchini use of PSA doubling time (170 pats)

27 74 yo pt, prostate adenocarcinoma treated by prostatectomy and radiotherapy. Moderately elevated PSA serum levels (1.7 ng/ml then 3.4 ng/ml 3 months later), but with a high velocity (6.5 ng/ml/year). FCH PET shows invaded juxta-aortic nodes. Service de Médecine Nucléaire, Hôpital Tenon

28 Positve FCH PET/CT vs Gleason score (n=172) 60 Gs<7. Gs=7. Gs> < 1 <1.5 < 2 < 3 < 4 >/=4 PSA ng/ml

29 Recurrent bone metastasis after prostatectomy and radiotherapy (from Dr Cimitan, Aviano) PSA: 0.53 ng/ml, Gs= 9

30 Lymph node recurrence after prostatectomy and radiotherapy (from Dr Cimitan, Aviano) PSA: 0.68 ng/ml, Gs= 9

31 En conclusion La TEP/TDM à la FCH, tout comme à la choline (11C), est très prometteuse dans le cancer de la prostate, L indication le plus étudiée est la récidive Un PHRC national sur la détection des récidives occultes vient de terminer ses inclusions (presque 200 en un an) : ICHOROPRO La place exacte dans la stratégie vis-à-vis de la TEP/TDM au fluorure (18F) et de l IRM reste à déterminer (FLUPROSTIC) La meilleure solution pourrait être la TEP/IRM