IMAGING with RADIOPHARMACEUTICALS Functional molecular specificity for disease
- Slides: 26
IMAGING with RADIOPHARMACEUTICALS Functional molecular specificity for disease detection and “follow-up” Durval C. Costa MD, MSc, Ph. D, FRCR Director Nuclear Medicine-Radiopharmacology Champalimaud Clinical Centre Champalimaud Foundation Text 1
IMAGING clinical practice & research 2
IMAGES in MEDICINE (resolution: spatial vs contrast/concentration) Method CT MRI MRSI SPECT PET HFUS Optical Minimum Detectable Size (Ø) 1 ~ 2 mm 7 mm (~3 mm at 3 T) 4 ~ 6 mm 3 ~ 5 mm < 1 mm 0. 02 mm Minimum Detected Molar Cells (n) m. M p. M 400, 000 1, 000 500, 000 300, 000 1000 3
IMAGES with RADIOPHARMACEUTICALS - Cellular functional Specificity - Fluorodeoxyglucose (FDG) is phosphorylated to FDG-6 -PO 4 by hexokinase. Since the activity of Fluorothymidine (FLT) is phosphorylated by thymidine glucose-6 -phosphatase is kinase to FLT-6 -PO 4 and negligible, FDG-6 -phosphate is accumulates in tumor cells. essentially trapped in tumor cells. Unfortunately it is also trapped in activated macrophages. Czernin J and Phelps ME. . Annu Rev Med, 2002; 53: 89 -112. It is described as a marker of cell proliferation. 4
IMAGES with RADIOPHARMACEUTICALS clinical and research applications Imaging and Molecular Medicine ü Radiopharmaceuticals for DIAGNOSIS ü Radiopharmaceuticals for THERAPY ü Radiopharmaceuticals for ASSESSMENT and MONITORING response to THERAPY ü Radioligands for R & D – new THERAPIES (pharmacokinetics and pharmacodynamics) 5
IMAGES with RADIOPHARMACEUTICALS Case 01 74 y old man; Radical prostatectomy 10 ys ago for carcinoma; Bone Scintigraphy – multiple bone metastases; ULTRASSOUN images – normal, i. e. sem no loco-regional recurrence; 17 -July-2006 Alkaline Phosphatase Acid Phosphatase Prostatic fraction 125 U/L 4, 3 U/L 0, 6 U/L (N 40 -150) (N 0, 0 -6, 5) (N < 2, 6) PSA 0, 33 ng/ml (N < 5) 0, 4 ng/ml (N 0, 0 -0, 5) (prostate specific antigen) Proteina C reactiva 6
IMAGES with RADIOPHARMACEUTICALS Case 01 24 -July-2006 7
IMAGES with RADIOPHARMACEUTICALS Case 01 Pathology from biopsy – Thyroid carcinoma; Total Thyroidectomy; 13 -November-2006 1 st IODO-131 THERAPY (7, 4 GBq, i. e. 200 m. Ci) 23 -July-2007 2 nd IODO-131 THERAPY (7, 4 GBq, i. e. 200 m. Ci) 8
RADIOPHARMACEUTICALS NUCLEAR/MOLECULAR MEDICINE PET-CT camera Gama camera Outpatient Inpatient Diagnosis Therapy Radiopharmaceuticals Generators Radionuclides Cyclotron Nuclear Reactor 9
RADIOPHARMACEUTICALS NUCLEAR/MOLECULAR MEDICINE Spatial resolution – detectable minimum lesion size!? 10
RADIOPHARMACEUTICALS Diagnose EARLY to IMPROVE Outcome! Function Clinical Ratings Time 11
RADIOPHARMACEUTICALS - PET Cost-Savings BENEFIT analyses! Ken A. Miles. An approach to demonstrating cost-effectiveness of diagnostic imaging modalities in Australia illustrated by positron emission tomography. Australasian Radiology, 2001; 45: 9 -18. 12
RADIOPHARMACEUTICALS - PET Cost-Savings BENEFIT analyses! 13
PET with FDG in ONCOLOGY UTILITY in CLINICS 1. Diagnosis and “grading” of malignant disease 2. Definition of disease extent staging and restaging 3. Identification and localisation of disease foci unknown primary (paraneoplastic syndromes) 4. Evaluation and monitoring of response to therapy 5. Identification of recurrent disease in comparison with “raising” tumour markers and anatomic/structural changes (CT and MR) 6. Guide for biopsy 7. Therapy guidance and “management” 14
PET with FDG in ONCOLOGY Overall results – sensitivity and specificity 1. Sensitivity - 84% (based on 18 402 patient studies) 2. Specificity - 88% (based on 14 264 patient studies) 3. Average management change across all aplications 30% (based on 5 062 patients) Sensitivity range 84% - 87% Specificity range 88% - 93% Accuracy range 87% - 90% Gambhir SJ, Czernin J, Schwimmer J, et al. A Tabulated Summary of the FDG PET Literature. J Nucl Med, 2001; 42: 1 S-93 S. [www. snm. org] 15
RADIOPHARMACEUTICALS Distinction between TUMOUR and inflammation 21 consecutive pts (3 women and 18 men, age range 41 to 80 y) with suspected squamous head and neck cancer. FDG Fluorodeoxyglucose FDG +ve SCC Oral cavity FET +ve FET O-(2 -[18 F]fluoroethyl)-L-tyrosine FDG +ve Chronic inflammation Pauleit D, Zimmermann A, Stoffels G, et al. J. Nucl Med, 2006; 47: 251 -261. FET -ve 16
RADIOPHARMACEUTICALS The future requests planning … measures and ACTION 11 C 18 F 3 H 15 O Cyclotron and “Production Facility” Molecular Chemistry 17
RADIOPHARMACEUTICALS The future requests planning … measures and ACTION FDG AC 13 of 22 pts with serum PSA > 3 ng/m. L had positive AC PET findings. 11 C -Acetate 77 -y-old man with PSA relapse and serum PSA value of 10. 5 ng/m. L 8 y after radical prostatectomy and 5 y after salvage external-beam radiation therapy. Histologic diagnosis showed Gleason score of 8 at surgery. CT scan negative. Oyama N, et al. J Nucl Med, 44 (4): 549 -555; 2003 Only 1 of 24 pts with serum PSA ≤ 3 ng/m. L had positive findings. 18
RADIOPHARMACEUTICALS … differential diagnosis of DEMENTIA AD Accuracy = 0. 778 (Exatidão = 0. 778) FTD Accuracy = 0. 875 (Exatidão = 0. 875) 19
RADIOPHARMACEUTICALS … labelling β-Amyloid pathology “in vivo”. 18 F-florbetapir (18 FAV-45) Benzothiazole 11 C - 6 -OH-BTA-1 (also known as 11 C - PIB) Binds to Aβ 1 -40 and Aβ 1 -42 fibrils Stilbene 11 C -SB-13 99 Tcm-MAMA-chrysamine (analog of Congo red) G 18 F-flutemetamol (18 FGE 067) 18 F-florbetaben (18 F-BAY 94 -9172) Labels Aβ 10 -43 20
RADIOPHARMACEUTICALS of disease - positive markers … labelling β-Amyloid pathology “in vivo”. 11 C-PIB N-Methyl-11 C-2 -(4´-methylamino-phenyl)-6 -hydroxy-benzothiazole or 11 C-6 -OH-BTA-1 Average radiochemical yield - 20%; Synthesis time - 45 min; Radiochemical purity - 98%. Ng S, et al. J Nucl Med 2007; 48: 547 -552. 21
RADIOPHARMACEUTICALS … imaging neuropathology “in vivo”. KS, 62 y old male; bil. tremor, rigity, akinesia, no falls, no visual hallucinations H & Y=3. 0; MMSE=27/30; CAMCOG=101/107 123 I-FP-CIT 123 I-IBZM dopamine D 2 post-synaptic receptor marker pre-synaptic transporter marker R INM Idiopathic Parkinson’s Disease (IPD) 22
RADIOPHARMACEUTICALS … imaging neuropathology “in vivo”. A D N V E T Drug induced parkinsonism IPD INM DLB INM Schizophrenia + PD AD= Alzheimer’s disease; DLB= dementia with Lewy bodies; ET= Essential benign tremor; IPD= idiopathic Parkinson’s disease; NV= normal volunteer 23
RADIOPHARMACEUTICALS … in Nuclear Cardiology – Myocardial Viability Coronary angiography confirms LMS occlusion (A), with patent RCA (B), rightto-left collateral circulation (C) and normal LV contractile function (D) 24
RADIOPHARMACEUTICALS … in Nuclear Cardiology – Myocardial Viability Patologias associadas Toxic Autonomous Adenoma of the THYROID Multiple pulmonary emboli 25
RADIOPHARMACEUTICALS … therapeutic APPLICATIONS Endocrinology Hyperthyroidism Ca Thyroid IODINE-131 Pheochromocytoma Paraganglioma Carcinoid IODINE-131 - m. IBG Intracavitary Synovectomy (microspheres) YTTRIUM-90 Resistent PAIN Ca Prostate Possibly others STRONTIUM-89 SAMARIUM-153 26
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