Download Radioisotopes for staging and follow

Radioisotopes for staging and
follow-up of prostate cancer
F. Scopinaro
Specific Radiotracers
Gamma ray emitters
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•
•
111In
capromab
111In octreotide
99mTc Tyr-octr. (more
than one tracer)
• 99mTc Bombesin
Positron emitters
•
•
11C
Choline
68 Ga Bombesin
111In
Capromab
• Rationale: 111In labelled anti MPSA
Monoclonal antibody
• Use: Staging and to lesser extent
radioguided surgery
• Results ( mainly american): 60 to 80%
sensitivity,incomplete specificity
111In/99mTc
and 123I peptide agonists
Peptides directed towards Gprotein coupled receptors
•
•
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•
Octreotide
octreotate
Tyr-octreotide
Bombesin
G-PROTEIN COUPLED RECEPTORS
Choline
-
IGF-I
1.
Somatostatine
Phosphorylation site
IGF-IR
Plasma membrane
choline
Y-P
P-Y
+
Ε2
αER
Ε2
αER
Gene
transcription
Cell division
2.
Bombesin
SSR 1,2,5
BNS 1,2,3
Cell nucleus
B.
2.
-
+
+
Endocytosis and recycling of cell surface
receptors
Cell surface receptor
GRP-R
recycling
endocytosis
New
Synthesis
Coated vesicle
endosomes
degradation
Golgi
Cell membrane
Figure 2.
lysosomes
nucleus
Labelled Amphibian BN: peptide structure ( Demokritos Natl.center)
99mTc[Leu13]
Bombesin (99mTc BN)
Cys-Aca-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-HisLeu-Met-NH2
Spacer arm;
Aca:Amino
esanoic acid
N terminal changed
in: Cys
labelling
Tc
Binding-to-receptor site
99mTc
BN is a labelled amphibian bombesin; it shows actions of:
neurotrasmitter, releasing factor, morphogen, tum. growth factor
Bombesin (BN) receptors
Brain
Outside Brain
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•
•
•
•
• Smooth muscle of
colon
• Gastrin secr. Cells
• Epithelial cancers
(breast, prostate,
colon)
• Stem cells
(unpublished data)
Thalamus
Amigdala
Hippocampus
Olphactory areas
Brain stems
Glandular and neuroendocrine
Prostate cancer
• Gland. Prostate cancer: Overexpression
of Bombesin receptors: NMB preferring
or BNS 1( 5 to 10 %), GRP preferring or
BNS 2 ( 80 to 90%), orphan BNS 3 (3 to
10), SSR1 and SSR5
• Neuroendocrine prostate cancer: SSR
subtype 2.
• others?
Prostate cancer with inconclusive Phase-Array NMR study:
diagnosis with 99mTc Bombesin SPECT.
B
P
B
U
U
MRI
BN SPECT
FUSION IMAGE
P: Prostate; B: Bladder; U: Urethra
Prostate cancer
Accepted for publlication, Eur.J. Nucl. Med mol Im, 18 june 2003
111In
Bladder
Prostate
Bladder
Prostate
Octreotide SPECT: prostate carcinoma
TRANSAXIAL SLIDES
MRI + 99mTc BN
R
99mTc
BN
L
Prostate cancer
111
In octreotide SPECT: negative findings
Results ( at the moment)
• 22 patients with PSA 4,1 to 10 ng/ml, 14
cancers
• 99mTc BN: Se= 100%; Sp= 100% ( 22
patients, 14 with final diagnosis of cancer )
• Uptake of 111In octreotide: 2 patiens out of 8
(10 out of the 14 patients with positive BN
SPECT)
Staging (lymph nodes)
• N staging in prostate cancer is difficult with
current imaging methods, including 18F DFG
PET
• 11C Choline PET and Choline/acetate NMR
spectroscopy are effective though not easily
available
• Detection of invaded lymph nodes can open a
new field in radioisotope guided surgery
99mTc BN
SPECT
Ca Prostata, 1
linfonodo
Otturatorio invaso
Linfonodo
Ca Prost.
Ca
Prostate Ca, 2
invaded nodes
(withdrawn with
radio guided
surgery )
Linfonodi
99mTc
BN, planar
reference for
SPECT
DFG PET
Radioguided surgery with portable high resolution imaging device
Radio guided surgery: Lymph
node image during operation
Results ( at the moment)
• Nine patients with inconclusive findings at
CT and NMRI before operation: detection
of invasion, 100% Sp (surgical and
pathological validation)
• two patients successfully operated with
radioguided surgery
Distant metastases
• Bone scan easily detects bone metastases
metastases: it is cheap and everywere
available
• Neuroendocrine shift can be detected on
blood with RIA chromogranine assay. This
method does not localise shifts
• BN and SS detect and localise the shift
Prostate cancer patient
99mTc MDP bone scan:
Diffuse metastatic bone uptake
CHEST, PLANAR SCAN
99mTc
BN
111In
Octreotide
Ant.
Post
met
99mTcBN,
whole body scan,
Patient with
metastases on bone
and soft tissue
met
99mTc
EDDA-HYNIC Tyr-OCTEOTIDE
distant soft tissue metastases with
neuroendocrine shift
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EDDA-HYNIC Tyr Octreotide, 40 min after I.V. administration
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Kidney
MET
Results (very Preliminar, only 5
patients with both tracers)
BN and 111In octreotide, as well as
99mTc Tyr-Octreotide are able to detect the
neuroendocrine shift of metastases. These
tracers are also able to detect soft tissue
metastases
• When neuroendocrine shift occurs it does
not affect all the metastases.
•
99mTc
Conclusions
• The use of 99mTc BN for diagnosis, staging
and follow-up of prostate cancer is still a
matter of research. Results are very
promising but have to be confirmed
• 99mTc BN is very promising for radioguided
surgery
• The uptake of 99mTc BN and 111In
octreotide is probably a method for
addressing therapy
Radiofarmaci con informazione complessa: bombesina/ adenoma
prost. Scintigrafia negativa
Radiofarmaci a informazione biologica complessa: Bombesina/Ca prostata
Gastrinoma in
a patient with
atrophic
gastritis and
high basal
secretin