IMAGES with RADIOPHARMACEUTICALS

Report
IMAGING with RADIOPHARMACEUTICALS
Functional molecular specificity for
disease detection and “follow-up”
Durval C. Costa
MD, MSc, PhD, FRCR
Director
Nuclear Medicine-Radiopharmacology
Champalimaud Clinical Centre
Champalimaud Foundation
Text
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IMAGING
clinical practice & research
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IMAGES in MEDICINE
(resolution: spatial vs contrast/concentration)
Method
CT
MRI
MRSI
SPECT
PET
HFUS
Optical
Minimum Detectable
Size (Ø)
1 ~ 2 mm
1 ~ 2 mm
7 mm (~3 mm at 3T)
4 ~ 6 mm
3 ~ 5 mm
< 1 mm
0.02 mm
Minimum Detected
Molar
Cells (n)
mM
pM
pM
400,000
400,000
1,000,000
500,000
300,000
100,000
1000
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IMAGES with RADIOPHARMACEUTICALS
- Cellular functional Specificity -
Fluorodeoxyglucose (FDG) is
phosphorylated to FDG-6-PO4 by
hexokinase. Since the activity of
Fluorothymidine (FLT) is
phosphorylated by thymidine
glucose-6-phosphatase is
kinase to FLT-6-PO4 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.
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IMAGES with RADIOPHARMACEUTICALS
clinical and research applications
Imaging and Molecular Medicine

Radiopharmaceuticals for DIAGNOSIS

Radiopharmaceuticals for THERAPY

Radiopharmaceuticals for ASSESSMENT and
MONITORING response to THERAPY

Radioligands for R & D – new THERAPIES
(pharmacokinetics and pharmacodynamics)
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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
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IMAGES with RADIOPHARMACEUTICALS
Case 01
24-July-2006
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IMAGES with RADIOPHARMACEUTICALS
Case 01
Pathology from biopsy – Thyroid carcinoma; Total Thyroidectomy;
13-November-2006
1st IODO-131 THERAPY
(7,4 GBq, i.e. 200 mCi)
23-July-2007
2nd IODO-131 THERAPY
(7,4 GBq, i.e. 200 mCi)
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RADIOPHARMACEUTICALS
NUCLEAR/MOLECULAR MEDICINE
PET-CT
camera
Gama
camera
Outpatient
Inpatient
Diagnosis
Therapy
Radiopharmaceuticals
Generators
Radionuclides
Cyclotron
Nuclear Reactor
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RADIOPHARMACEUTICALS
NUCLEAR/MOLECULAR MEDICINE
Spatial resolution – detectable minimum lesion size!?
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RADIOPHARMACEUTICALS
Diagnose EARLY to IMPROVE Outcome!
Function
Clinical Ratings
Time
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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.
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RADIOPHARMACEUTICALS - PET
Cost-Savings BENEFIT analyses!
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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”
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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: 1S-93S. [www.snm.org]
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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-[18F]fluoroethyl)-L-tyrosine
FDG +ve
Chronic
inflammation
Pauleit D, Zimmermann A, Stoffels G, et al. J. Nucl Med, 2006; 47: 251-261.
FET -ve
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RADIOPHARMACEUTICALS
The future requests planning … measures and ACTION
11C
18F
3H
15O
Cyclotron and “Production Facility”
Molecular Chemistry
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RADIOPHARMACEUTICALS
The future requests planning … measures and ACTION
FDG
AC
13 of 22 pts with
serum PSA > 3ng/mL
had positive AC PET
findings.
11C
-Acetate
77-y-old man with PSA relapse and serum PSA value
of 10.5 ng/mL 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 ≤ 3ng/mL
had positive findings.
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RADIOPHARMACEUTICALS
… differential diagnosis of DEMENTIA
AD
FTD
AccuracyROC=AD0.778
vs Ctr parietotemporal, multiple
head cameras
(Exatidão = 0.778)
Accuracy = 0.875
(Exatidão = 0.875)
ROC FLD vs Ctr frontal, all studies
Accuracy= 0.875
Accuracy= 0.778
1.00
1.00
0.90
0.90
Cut off point=0.89
Specificity=48%
Sensitivity=84%
sensitivity
0.70
0.60
0.70
Cut off point 0.82
Specificity= 75%
Sensitivity=66%
0.50
0.40
0.60
0.40
0.30
0.20
0.20
0.10
0.10
0.10
0.20
0.30
0.40
0.50
0.60
1-specificity
0.70
0.80
0.90
1.00
Cut off point 0.76
Specificity= 85%
Sensitivity=76%
0.50
0.30
0.00
0.00
Cut off point=0.8
Specificity=68%
Sensitivity=87%
0.80
sensitivity
0.80
0.00
0.00
0.10
0.20
0.30
0.40
0.50
0.60
0.70
0.80
0.90
1.00
1-specificity
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RADIOPHARMACEUTICALS
… labelling β-Amyloid pathology “in vivo”.
18F-florbetapir
(18FAV-45)
Benzothiazole 11C - 6-OH-BTA-1
(also known as 11C - PIB)
Binds to Aβ 1-40 and Aβ 1-42 fibrils
Stilbene 11C -SB-13
99Tcm-MAMA-chrysamine
(analog of Congo red)
G
18F-flutemetamol
(18FGE067)
18F-florbetaben
(18F-BAY94-9172)
Labels Aβ 10-43
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RADIOPHARMACEUTICALS
of disease
- positive markers
… labelling β-Amyloid pathology “in vivo”.
11C-PIB
N-Methyl-11C-2-(4´-methylamino-phenyl)-6-hydroxy-benzothiazole or
11C-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.
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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
123I-FP-CIT
123I-IBZM
dopamine D2
post-synaptic
receptor
marker
pre-synaptic
transporter
marker
R
INM
Idiopathic Parkinson’s Disease (IPD)
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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
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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)
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RADIOPHARMACEUTICALS
… in Nuclear Cardiology – Myocardial Viability
Patologias associadas
Toxic Autonomous Adenoma
of the THYROID
Multiple pulmonary emboli
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RADIOPHARMACEUTICALS
… therapeutic APPLICATIONS
Endocrinology
Hyperthyroidism
Ca Thyroid
IODINE-131
Pheochromocytoma
Paraganglioma
Carcinoid
IODINE-131 - mIBG
Intracavitary
Synovectomy
(microspheres)
YTTRIUM-90
Resistent PAIN
Ca Prostate
Possibly others
STRONTIUM-89
SAMARIUM-153
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