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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
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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 lt 1 mm 0.02 mm
Minimum Detected Molar Cells (n) mM 400,000 400,
000 1,000,000 pM 500,000 pM 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
glucose-6-phosphatase is negligible,
FDG-6-phosphate is essentially trapped in tumor
cells. Unfortunately it is also trapped in
activated macrophages.
Fluorothymidine (FLT) is phosphorylated by
thymidine kinase to FLT-6-PO4 and accumulates in
tumor cells. It is described as a marker of cell
proliferation.
Czernin J and Phelps ME.. Annu Rev Med, 2002 53
89-112.
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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 Alkalin
e Phosphatase 125 U/L (N 40-150) Acid
Phosphatase 4,3 U/L (N 0,0-6,5) Prostatic
fraction 0,6 U/L (N lt 2,6) PSA (prostate
specific antigen) 0,33 ng/ml (N lt 5) Proteina C
reactiva 0,4 ng/ml (N 0,0-0,5)
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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)
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RADIOPHARMACEUTICALS NUCLEAR/MOLECULAR MEDICINE
Diagnosis
Therapy
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RADIOPHARMACEUTICALS NUCLEAR/MOLECULAR MEDICINE
Spatial resolution detectable minimum lesion
size!?
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RADIOPHARMACEUTICALS Diagnose EARLY to IMPROVE
Outcome!
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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

• Diagnosis and grading of malignant disease
• Definition of disease extent
• staging and restaging
• Identification and localisation of disease foci
• unknown primary (paraneoplastic syndromes)
• Evaluation and monitoring of response to therapy
• Identification of recurrent disease in comparison
  with raising tumour markers and
  anatomic/structural changes (CT and MR)
• Guide for biopsy
• Therapy guidance and management

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PET with FDG in ONCOLOGY Overall results
sensitivity and specificity

• Sensitivity - 84 (based on 18 402 patient
  studies)
• Specificity - 88 (based on 14 264 patient
  studies)
• 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
FET O-(2-18Ffluoroethyl)-L-tyrosine
Chronic inflammation
Pauleit D, Zimmermann A, Stoffels G, et al. J.
Nucl Med, 2006 47 251-261.
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RADIOPHARMACEUTICALS The future requests planning
measures and ACTION
18F
11C
15O
3H

Cyclotron and Production Facility
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RADIOPHARMACEUTICALS The future requests planning
measures and ACTION
13 of 22 pts with serum PSA gt 3ng/mL had positive
AC PET findings. Only 1 of 24 pts with serum
PSA 3ng/mL had positive 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
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RADIOPHARMACEUTICALS differential diagnosis
of DEMENTIA
AD
FTD
Accuracy 0.778 (Exatidão 0.778)
Accuracy 0.875 (Exatidão 0.875)
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RADIOPHARMACEUTICALS labelling ß-Amyloid
pathology in vivo.
18F-florbetapir (18FAV-45) 18F-flutemetamol (18FG
E067) 18F-florbetaben (18F-BAY94-9172)
Benzothiazole 11C - 6-OH-BTA-1 (also known as 11C
- PIB) Binds to Aß 1-40 and Aß 1-42 fibrils
Stilbene 11C -SB-13
99Tcm-MAMA-chrysamine G (analog of Congo
red) Labels Aß 10-43
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RADIOPHARMACEUTICALS - positive markers of
disease labelling ß-Amyloid pathology in vivo.
11C-PIB N-Methyl-11C-2-(4-methylamino-phenyl)-6-h
ydroxy-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.

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RADIOPHARMACEUTICALS imaging neuropathology
in vivo.
AD Alzheimers disease DLB dementia with Lewy
bodies ET Essential benign tremor IPD
idiopathic Parkinsons disease NV normal
volunteer
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RADIOPHARMACEUTICALS in Nuclear Cardiology
Myocardial Viability

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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