Transcript Kotka-Garske-111In-D..

Diagnostic imaging with
111In-DTPA-octreotide:
Clinical impact on the management of
patients with neuroendocrine tumours
Ulrike Garske MD
Specialist in oncology, nuclear and internal
medicine
Kotka May 2010
Overview
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Neuroendocrine tumours: clinic and treatment
Indications for imaging
Somatostatin
111In-DTPA-octreotide (OctreoScan®)
Imaging
 Normal Findings
 Uptake scale
 Typical and unusual findings
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Some patients, that you have sent to us for treatment
Thank you
Neuroendocrine tumours
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A small tumour group, with lots to learn
from!
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During the last decade, an evolving model for
designing and studying tracers in nuclear
imaging and therapy
Neuroendocrine tumours
Gastro-entero-pancreaticoduodenal tumours (GEP-NETs)
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”Carcinoids”: derived from embryonal foregut, midgut
and hindgut
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Foregut och midgut carcinoids: Production of
5-HIAA (classic carcinoid syndrom: flushing,
palpitation, diarrhea)
Endocrine pankreaticoduodenal tumours (EPTs):
functioning or non-functioning
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Different associated hormonal syndroms
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Gastrin, insulin, glucagon, VIP, somatostatin,
ACTH….
Neuroendocrine tumours
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Pheochromocytomas /paragangliomas
Medullary thyroid carcinomas
Neuroendocrine cancers/ neuroendocrine
tumours of unknown origin
…………..many rare entities
Treatment overview
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Surgery
Local destruction of livermetastases
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Leverembolisation
Radiofrequency ablation
Biological treatment (alpha-Interferon,
Somatostatinanalogs)
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Chemotherapy
Radiation
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External Beam
Brachytherapy of livermetastases (SIR-spheres®)
Peptide receptor radionuclide therapy
(PRRT)
Indications for diagnostic imaging
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Staging of recently diagnosed patients
Finding small tumours: important in case of
significant hormone production (pancreas) , or to
rule out extrahepatic disease prior to
livertransplantation
Receptor status before chosing therapy
Follow-up of therapy
If finding small tumours is
important…..
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…Maybe PET/CT is your choice
11C-5-HTP
(HTP)
C
11
11C-5-hydroxytryptophan
If the receptor status is important…..
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Imaging with somatostatin
analogs!
Somatostatin
Somatostatin
Somatostatin
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Regulatory hormone, that
 Inhibits growth hormone
 Inhibits/suppresses release of a row of
gastrointestinal hormones (VIP, glucagon,
cholecystokinin, gastrin, motilin, secretin….)
 Suppresses the exocrine function of the
pancreas
 Inhibits TSH
Octreotide (Sandostatin®)
Somatostatin receptors
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5 subtypes (sstr1- sstr5)
Sstr2 predominant in neuroendocrine tumours,
followed by sst5
Octreotide somatostatin analog predominantly
used in the clinic (Sandostatin®, Sandostatin
LAR®), predominant affinity for sstr2 and 5
Golden standard för sstr- diagnostic in nuclear
medicine: OctreoScan® (111In-DTPA-octreotide)
Normal distribution
Physiological
uptake in:
Pituitary
Thyroid
Liver
Spleen
Kidneys
Adrenals
Gut
Anterior
Posterior
OctreoScan® imaging
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Whole body scan: Scanning time (at least 30min)
SPECT/CT: so much better information
Activity 200MBq for adults; one kit per patient
Imaging after 24 hrs sufficient , SPECT/CT and patient
preparation important
Laxation:
Toilax® (Bisacodyl)
 2 tabl. à 5mg noon and evening on day of injection
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klysma Toilax® morning of examination day
Liquid food 12.00 noon inj. day until examination is
finished
Intensity of uptake
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Arbitrary scale (according to Krenning): uptake in
relation to liver uptake
0: no uptake
1: weak uptake, less than liver
2: moderate uptake equivalent to liver
3: intense uptake, higher than liver
4:very intense uptake, much higher than liver, more
intense than spleen/kidneys
OctreoScan® 1996: both diagnostics and
therapy
Normal uptake
Grade 3-4
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Grade 1
Grade 3
Grade 4: Patient with hindgut
carcinoid
Imaging: Midgut carcinoid
Static
posterior
Static
anterior
?
ant
post
Tornado sign
Massive mesenterial dissemination
……and one thoracic lymph node
Midgut High proliferation
Ant
post
ant
post
Cardiac metastases
Right liver lobe previously treated
with embolization
Left liver lobe: untreated metastases
Imaging: Insulinoma
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Insulinomas: predominant pancreatic endocrine
tumour group
Better prognosis than other GEP NETs
Excellent surgical curation rate, if localized
express in only 50% sstr2
Malignant insulinomas may have higher expression
of sstr2
73yr-old lady with hypoglycemic fits
Isolated insulinoma in ectopic
pancreatic tissue
Patient alive and well……..
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Symptom free now 7 years after surgery
Celebrating her 80th birthday this year
Malignant Insulinoma
Malignant Insulinoma
Malignant Insulinoma
Follow up of therapy
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Somatostatin receptor density
may vary in different metastases in the same
patient
 May change over time
 Somatostatin receptor scintigraphy should
only be interpreted together with radiological
information
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56y-old lady, atypical bronchial
carcinoid
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Previously pulmectomy
3 years later pain in the back
Treatment with temozolomide (Temodal®)
Follow-up with OctreoScan®: not a
given indication….
Baseline
after 3
6
9 courses
…but it may help to interprete your
CT-findings
Cave: Receptor up-regulation
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Treatment can change receptor expression
New uptake does not necessarily need to represent
new lesions.
Example of a patient with malignant
pheochromocytoma
OctreoScan®
OctreoScan®
123I
MIBG
Malignant Pheochromocytoma
Diagnostic imaging
123I-MIBG
111In-Oscan
October 08
Therapy
131I-MIBG
177Lu-DOTA-tate
October 08
April 09
Treatment
Treatment with radiolabelled
somatostatin analogs
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A renaissance for imaging with 111In-DTPAoctreotide?!!
Octreotide
Lutetium
177Lu-DOTA-Tyr3-Octreotate
111In-DTPA-octreotide
177Lu-DOTA-octreotate
24h
ant
post
ant
post
Diagnostic images and therapy control:
tumour-to-background
Oscan 24h
Lu 0h
24h
96h
168h
Treatments with 177Lu-DOTA-octreotate
250
Antal behandlingar
200
150
100
50
0
2005
2006
2007
2008
2009
Hindgut carcinoid: therapy 1-4
Effect of therapy over time
Feb 09
April 09
July 09
Aug 09
Jan 10
Ther 1
Ther 6
Glomerular filtration rate before therapy
Before
ther1
ther2
ther3
ther4 ther5 ther6
Therapy effects 2:
Patient with hindgut carcinoid
ther 1 ther 2
ther 3
ther 4
ther 5
Anterior view , 177Lu-DOTA-octreotate 24 h pi
ther 6
Therapy 1
Therapy 3
CT-interpretation: take advantage of
your scintigraphy!
Therapy 1
Therapy 6
Therapy 1
Therapy 6
177Lu-DOTA-octreotate
therapy
Results from Rotterdam
Result 3 months after completed therapy(n=310):
CR
5
(2%)
PR
86
(28%)
MR
51
(16%)
SD
107
(35%)
PD
61
(20%)
46%
4% with SD or MR improved further after 6 months
5% with SD or MR improved further after 12 months
Kwekkeboom et al, JCO, 2008
Thank you to
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Mattias Sandström and collegue hospital physicists
Prof emeritus Hans Lundqvist (Radiophysics)
Prof Barbro Eriksson och Prof Kjell Öberg, endocrine oncology
Doc Dan Granberg
Prof Anders Sundin
Collegues an staff at the department of nuclear medicine,
Uppsala Academical Hospital
Research collegues and friends at Rudbecklaboratoriet
Med kand Daniel Lindholm
Our patients, and……….
… Thank You for inviting me to
beautiful Finland !