Diagnostic imaging Diagnostic imaging with 111In-DTPA- with 111In-DTPA- octreotide: octreotide: Clinical impact on the Clinical impact on the management of patients with management of patients with neuroendocrine tumours neuroendocrine tumours Ulrike Garske MD Ulrike Garske MD Specialist in oncology, nuclear and Specialist in oncology, nuclear and internal medicine internal medicine Kotka May 2010 Kotka May 2010
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Diagnostic imaging with 111In-DTPA-octreotide: Clinical impact on the management of patients with neuroendocrine tumours Ulrike Garske MD Specialist in.
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Diagnostic imaging with Diagnostic imaging with 111In-DTPA-octreotide:111In-DTPA-octreotide:
Clinical impact on the management of Clinical impact on the management of patients with neuroendocrine tumourspatients with neuroendocrine tumours
Ulrike Garske MDUlrike Garske MD
Specialist in oncology, nuclear and internal Specialist in oncology, nuclear and internal medicinemedicine
Kotka May 2010Kotka May 2010
OverviewOverview
Neuroendocrine tumours: clinic and treatmentNeuroendocrine tumours: clinic and treatment Indications for imagingIndications for imaging SomatostatinSomatostatin 111111In-DTPA-octreotide (OctreoScan®)In-DTPA-octreotide (OctreoScan®)
ImagingImaging Normal FindingsNormal Findings Uptake scaleUptake scale Typical and unusual findingsTypical and unusual findings
Some patients, that you have sent to us for treatment Some patients, that you have sent to us for treatment Thank youThank you
Neuroendocrine tumoursNeuroendocrine tumours
A small tumour group, with lots to learn A small tumour group, with lots to learn from!from!
During the last decade, an evolving model for During the last decade, an evolving model for designing and studying tracers in nuclear designing and studying tracers in nuclear imaging and therapyimaging and therapy
””Carcinoids”: derived from embryonal foregut, midgut Carcinoids”: derived from embryonal foregut, midgut and hindgutand hindgut Foregut och midgut carcinoids: Production of Foregut och midgut carcinoids: Production of
External BeamExternal Beam Brachytherapy of livermetastases (SIR-spheres®)Brachytherapy of livermetastases (SIR-spheres®) Peptide receptor radionuclide therapy (PRRT)Peptide receptor radionuclide therapy (PRRT)
Indications for diagnostic imaging Indications for diagnostic imaging
Staging of recently diagnosed patientsStaging of recently diagnosed patients Finding small tumours: important in case of Finding small tumours: important in case of
significant hormone production (pancreas) , or to significant hormone production (pancreas) , or to rule out extrahepatic disease prior to rule out extrahepatic disease prior to livertransplantationlivertransplantation
Receptor status before chosing therapyReceptor status before chosing therapy Follow-up of therapyFollow-up of therapy
If finding small tumours is If finding small tumours is important…..important…..
……Maybe PET/CT is your choiceMaybe PET/CT is your choice
11C-5-HTP(HTP)
11C
11C-5-hydroxytryptophan
If the receptor status is important…..If the receptor status is important…..
Imaging with somatostatin Imaging with somatostatin analogs! analogs!
SomatostatinSomatostatin
SomatostatinSomatostatin
SomatostatinSomatostatin
Regulatory hormone, thatRegulatory hormone, that Inhibits growth hormoneInhibits growth hormone Inhibits/suppresses release of a row of Inhibits/suppresses release of a row of
5 subtypes (sstr1- sstr5)5 subtypes (sstr1- sstr5) Sstr2 predominant in neuroendocrine tumours, Sstr2 predominant in neuroendocrine tumours,
followed by sst5followed by sst5 Octreotide somatostatin analog predominantly Octreotide somatostatin analog predominantly
used in the clinic (Sandostatin®, Sandostatin used in the clinic (Sandostatin®, Sandostatin LAR®), predominant affinity for sstr2 and 5LAR®), predominant affinity for sstr2 and 5
Golden standard för sstr- diagnostic in nuclear Golden standard för sstr- diagnostic in nuclear medicine: OctreoScan® (medicine: OctreoScan® (111111In-DTPA-octreotide)In-DTPA-octreotide)
Normal distributionNormal distribution
Anterior Posterior
Physiological uptake in:
PituitaryThyroidLiverSpleenKidneysAdrenalsGut
OctreoScan® imagingOctreoScan® imaging
Whole body scan: Scanning time (at least 30min)Whole body scan: Scanning time (at least 30min) SPECT/CT: so much better informationSPECT/CT: so much better information Activity 200MBq for adults; one kit per patientActivity 200MBq for adults; one kit per patient Imaging after 24 hrs sufficient , SPECT/CT and patient Imaging after 24 hrs sufficient , SPECT/CT and patient
preparation importantpreparation important Laxation:Laxation: Toilax® (Bisacodyl) Toilax® (Bisacodyl)
2 tabl. à 5mg noon and evening on day of injection2 tabl. à 5mg noon and evening on day of injection
klysma Toilax® morning of examination dayklysma Toilax® morning of examination day Liquid food 12.00 noon inj. day until examination is Liquid food 12.00 noon inj. day until examination is
finishedfinished
Intensity of uptakeIntensity of uptake
Arbitrary scale (according to Krenning): uptake in Arbitrary scale (according to Krenning): uptake in relation to liver uptakerelation to liver uptake
0: no uptake0: no uptake 1: weak uptake, less than liver1: weak uptake, less than liver 2: moderate uptake equivalent to liver2: moderate uptake equivalent to liver 3: intense uptake, higher than liver3: intense uptake, higher than liver 4:very intense uptake, much higher than liver, more 4:very intense uptake, much higher than liver, more
intense than spleen/kidneysintense than spleen/kidneys
OctreoScan® 1996: both diagnostics and OctreoScan® 1996: both diagnostics and therapytherapy
Normal uptakeNormal uptake
Grade 1
Grade 3-4
Grade 3
Grade 4: Patient with hindgut Grade 4: Patient with hindgut carcinoidcarcinoid
Better prognosis than other GEP NETsBetter prognosis than other GEP NETs Excellent surgical curation rate, Excellent surgical curation rate, if localizedif localized express in only 50% sstr2express in only 50% sstr2 Malignant insulinomas may have higher expression Malignant insulinomas may have higher expression
of sstr2of sstr2
73yr-old lady with hypoglycemic fits73yr-old lady with hypoglycemic fits
Isolated insulinoma in ectopic Isolated insulinoma in ectopic pancreatic tissuepancreatic tissue
Patient alive and well……..Patient alive and well……..
Symptom free now 7 years after surgerySymptom free now 7 years after surgery Celebrating her 80th birthday this yearCelebrating her 80th birthday this year
Malignant InsulinomaMalignant Insulinoma
Malignant InsulinomaMalignant Insulinoma
Malignant InsulinomaMalignant Insulinoma
Follow up of therapyFollow up of therapy
Somatostatin receptor densitySomatostatin receptor density may vary in different metastases in the same may vary in different metastases in the same
patientpatient May change over timeMay change over time Somatostatin receptor scintigraphy should Somatostatin receptor scintigraphy should
only be interpreted together with radiological only be interpreted together with radiological informationinformation
Previously pulmectomyPreviously pulmectomy 3 years later pain in the back3 years later pain in the back Treatment with temozolomide (Temodal®)Treatment with temozolomide (Temodal®)
Follow-up with OctreoScan®: not a Follow-up with OctreoScan®: not a given indication….given indication….
Baseline after 3 6 9 courses
……but it may help to interprete your but it may help to interprete your CT-findingsCT-findings
Treatment can change receptor expressionTreatment can change receptor expression New uptake does not necessarily need to represent New uptake does not necessarily need to represent
new lesions.new lesions.
Example of a patient with malignant Example of a patient with malignant pheochromocytomapheochromocytoma
Effect of therapy over timeEffect of therapy over time
Feb 09 April 09 July 09 Aug 09 Jan 10
Ther 1Ther 1 Ther 6Ther 6
Glomerular filtration rate before therapyGlomerular filtration rate before therapy
Before ther1 ther2 ther3 ther4 ther5 ther6
Therapy effects 2: Therapy effects 2: Patient with hindgut carcinoidPatient with hindgut carcinoid
ther 1 ther 2 ther 3 ther 4 ther 5 ther 6
Anterior view , 177Lu-DOTA-octreotate 24 h pi
Therapy 1Therapy 1 Therapy 3Therapy 3
CT-interpretation: take advantage of CT-interpretation: take advantage of your scintigraphy!your scintigraphy!
Therapy 1Therapy 1 Therapy 6Therapy 6
Therapy 1Therapy 1 Therapy 6Therapy 6
177Lu-DOTA-octreotate therapyResults from Rotterdam
Kwekkeboom et al, JCO, 2008
Result 3 months after completed therapy(n=310):Result 3 months after completed therapy(n=310):
CRCR 55 (2%)(2%)
PRPR 8686 (28%)(28%) 46%46%
MRMR 5151 (16%)(16%)
SDSD 107107 (35%)(35%)
PDPD 6161 (20%)(20%)
4% with SD or MR improved further after 6 months
5% with SD or MR improved further after 12 months
Thank you toThank you to
Mattias Sandström and collegue hospital physicistsMattias Sandström and collegue hospital physicists Prof emeritus Hans Lundqvist (Radiophysics) Prof emeritus Hans Lundqvist (Radiophysics) Prof Barbro Eriksson och Prof Kjell Öberg, endocrine oncologyProf Barbro Eriksson och Prof Kjell Öberg, endocrine oncology Doc Dan GranbergDoc Dan Granberg Prof Anders SundinProf Anders Sundin Collegues an staff at the department of nuclear medicine, Collegues an staff at the department of nuclear medicine,
Uppsala Academical HospitalUppsala Academical Hospital Research collegues and friends at RudbecklaboratorietResearch collegues and friends at Rudbecklaboratoriet Med kand Daniel LindholmMed kand Daniel Lindholm Our patients, and……….Our patients, and……….
… … Thank You for inviting me to Thank You for inviting me to beautiful Finland !beautiful Finland !