Imaging and Therapy in Nuclear Medicine Jan de Swart PET and - - PowerPoint PPT Presentation

Imaging and Therapy in Nuclear Medicine

Jan de Swart

PET and SPECT

• Ultra high sensitivity (pM-nM), quantitative
• Tracer quantities (no pharmacological effect)
• Function over time:
• imaging of receptor expression, apoptosis and

angiogenesis, enzymatic activity, substrate metabolism, drug pharmacokinetics, DNA synthesis and (reporter) gene expression

• Early imaging, whole body and 3-D, non-

invasive

Photo Multiplier Tube

Human versus mouse

Human, approx.. 175 cm. and 65 kg Mouse, approx.. 10 cm. (without tail) and 10 gram

Much better resolution needed!

SPECT imaging

Object Intrinsic resolution NaI(Tl) PMT 1:1 projection

Conventional SPECT:

• Parallel-hole collimator, large FOV
• Spatial resolution: ~1cm

Object PMT NaI(Tl) magnifying projection Intrinsic resolution

Pinhole SPECT:

• Magnification, but small FOV
• Spatial resolution: ~1mm

Pinhole design

Pinhole collimator

Improved resolution

with parallel-hole SPECT with pinhole SPECT Resolution: 6 mm Sensitivity: 100 cps/MBq Resolution: < 1 mm Sensitivity: 600 cps/MBq

SPECT systems

MILabs VECTor5 SPECT/PET/CT/OI

Optical Imaging

Optical Imaging

Detection range of imaging modalities

Anatomy Physiology Metabolism Molecular X-Ray/CT US MRI Nuclear Optical Weissleder, Radiology 1999; 212: 609–614

Combination!

PET/SPECT

PET/CT

SPECT/MRI

SPECT: 99mTc-DMSA MRI: T2 weighted

PET Detection

PET System

Siemens Inveon

18FDG

Advantages of PET and SPECT

Contribution of micro-SPECT and -PET to science: – Partly replacement of sectioning, counting and autoradiography – Reduction of number of animals required – Dynamic and longitudinal imaging in intact animals – Contribution to understanding of gene functions – Acceleration of pharmaceutical development – Breakthroughs in areas like cardiology, neurosciences and

• ncology

PET versus SPECT

PET and SPECT both uses many radiolabelled compounds as molecular probes.

Advantages of PET:

• higher sensitivity
• use of physiol. tracers
• better quantification
• less noise

Advantages of SPECT tracers:

• have longer half-lives
• are cheaper
• more widely available
• multiple labelling studies
• higher resolution
• Dual isotope studies

Performing animal imaging

NanoSPECT/CT system Heating Isoflurane

• Equipped with heated rat- and mouse beds
• Connection for isoflurane anesthesia

18F-FDG

Glucose analog, hydroxyl group (-OH) is replaced by Fluor-18 (18F)

• Oncology
• Cardiology
• Neurology
• Inflammation

Influence of animal handling

MIP (@ 180°) White-Black: 0-15% max Bq/ml ∑ 90” scans shown

FDG IV iso IV awake IP iso IV awake 60min IV no fasting Fasted Yes Yes Yes No No Preheating 30° Yes Yes Yes No Yes Injection IV (iso) IV (awake) IP (iso) IV (awake) IV (iso) Method Cannula tail vein Needle tail vein Needle peritoneal Needle tail vein Cannula tail vein Awake after injection No No No 60’ No Scantime 90’ 90’ 90’ 30’ 90’

Organ function

125I 99mTc-MDP

Radionuclide – chelator – peptide

O N N N N COOH HOOC HOOC C

D-Phe - Cys - Tyr

N H

Lys

• Thr
• Cys

Thr(ol)- D-Trp

S S

111In 68Ga 177Lu

Octreotide

Peptide receptor imaging

Tumor cell

• 3. Internalization
• 2. Receptor binding
• 4. Visualization
• Peptide receptors over-expression on tumours

SST receptor

1. Intraveneus injection of radiolabeled peptide

radiolabelled peptide analog

PRS

Peptide Receptor Scintigraphy

111In,99mTc,…

low energy transfer high tissue penetration range Peptide Receptor Radionuclide Therapy

90Y,177Lu,…

high energy transfer low tissue penetration range

PRRT

225Ac…

[177Lu-DOTA]octreotate in small animals

278 MBq [177Lu-DOTA]octreotate 5 days after therapy (injection radiopeptide) 50 MBq [111In]Octreoscan 4h after injection 28 days after therapy