IMAGING with RADIOPHARMACEUTICALS
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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. Text. IMAGING clinical practice & research.

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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

< 1 mm

0.02 mm

Minimum Detected

Molar Cells (n)

mM400,000

400,000

1,000,000

pM500,000

pM300,000

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

Alkaline Phosphatase125 U/L(N 40-150)

Acid Phosphatase4,3 U/L(N 0,0-6,5)

Prostatic fraction0,6 U/L(N < 2,6)

PSA (prostate specific antigen)0,33 ng/ml(N < 5)

Proteina C reactiva0,4 ng/ml(N 0,0-0,5)


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IMAGES with RADIOPHARMACEUTICALS

Case 01

24-July-2006


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23-July-2007

2nd IODO-131 THERAPY

(7,4 GBq, i.e. 200 mCi)

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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PET-CT

camera

Gama

camera

Outpatient

Inpatient

Radiopharmaceuticals

Cyclotron

Generators

Radionuclides

Nuclear Reactor

RADIOPHARMACEUTICALS

NUCLEAR/MOLECULAR MEDICINE

Diagnosis

Therapy


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RADIOPHARMACEUTICALS

NUCLEAR/MOLECULAR MEDICINE

Spatial resolution – detectable minimum lesion size!?


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Function

Clinical Ratings

Time

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 range84% - 87%

  • Specificity range88% - 93%

  • Accuracy range87% - 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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    SCC

    Oral cavity

    FDG +ve

    FET +ve

    FDG +ve

    FET -ve

    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-[18F]fluoroethyl)-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

    11C

    18F

    3H

    15O

    Molecular Chemistry

    Cyclotron and “Production Facility”


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    FDG

    AC

    RADIOPHARMACEUTICALS

    The future requests planning … measures and ACTION

    13 of 22 pts with serum PSA > 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 β-Amyloid pathology “in vivo”.

    18F-florbetapir

    (18FAV-45)

    18F-flutemetamol

    (18FGE067)

    18F-florbetaben

    (18F-BAY94-9172)

    Benzothiazole11C - 6-OH-BTA-1

    (also known as 11C - PIB)

    Binds to Aβ 1-40 and Aβ 1-42 fibrils

    Stilbene11C -SB-13

    99Tcm-MAMA-chrysamine G

    (analog of Congo red)

    Labels Aβ 10-43


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    RADIOPHARMACEUTICALS - positive markers of disease… 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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    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

    Idiopathic Parkinson’s Disease (IPD)

    RADIOPHARMACEUTICALS

    … imaging neuropathology “in vivo”.

    INM


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    A D

    N V

    E T

    Drug induced

    parkinsonism

    IPD

    DLB

    Schizophrenia + PD

    RADIOPHARMACEUTICALS

    … imaging neuropathology “in vivo”.

    AD= Alzheimer’s disease; DLB= dementia with Lewy bodies; ET= Essential benign tremor; IPD= idiopathic Parkinson’s disease; NV= normal volunteer

    INM

    INM


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    Coronary angiography confirms LMS occlusion (A), with patent RCA (B), right-to-left collateral circulation (C) and normal LV contractile function (D)

    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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    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

    RADIOPHARMACEUTICALS

    … therapeutic APPLICATIONS


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