Molecular imaging

The lecture documents the basic utility of molecular imaging tools in radiology and nuclear medicine i.e. PET-CT

1. MOLECULAR
IMAGING

2. Molecular imaging
offers unique insights into the
human body that enable
physicians to personalize
patient care. In terms of
diagnosis, molecular imaging is
able to:
 provide information that is
unattainable with other imaging
technologies or that would
require more invasive
procedures such as biopsy or
surgery
 identify disease in its earliest
stages and determine the exact
location of a tumor, often before
symptoms occur or
abnormalities can be detected
with other diagnostic tests
SNMI

4. SYNTHESIS OF THE PET TRACERS

5. BIOLOGICAL MARKER
(PET PROBE)
18F-+ (labelling radiopharmaceitical agent) FDG

6. Glut 1 expression
A
A

7. BIOMARKERS

8. IMAGING PLATFORM
(PET/CT)

9. Biological tumour
TARGETS

10. TUMOUR METABOLISM
METABOLISM
AMINO ACID
METABOLISM
GLUCOSE
UTILISATION
CELLULAR
PROLIFERATION

11. FCL
FCL
FDG
FET
FLT
FL
Nucelotide
syntehsis

12. PET
TRACERS
PET PROBE BIOMARKER USE
18 F
18 F-FDG
GLUCOSE
METABOLISM
Lymphoma
Head & Neck ca
NSCLC, melanoma,
colon ca, Cardiac
Viability
18-F-FET AMINO ACID
METABOLISM
CANCER
(BRAIN-glioma)
18 F-FLT TISSUE
PROLIFERATION
CANCER
(BRAIN)
18-F-FMISO/FAZA TISSUE HYPOXIA CANCER
(GIST/SARCOMA)
18-F-FCH STEROL
PROLIFERATION
CANCER
(Prostate)
68 Ga 68-Ga-Octreotate
TUMOUR RECEPTOR
OVEREXPRESSION
CANCER
(NET)
82-Rb
( PERFUSION) Myocardial Perfusion

13. 18-F-FDG (glucose metabolism)
58-year0old man –staging of NSCLC

14. Semiquatitative marker: SUV
–= tracer activity / injected dose normalized to
body weight.
•SUV was a significant and independent
predictorof local control and disease-free
survival . Tatsuo Torizukaet al AJR2009; 192:W156-W160

15. Tumour FDGroles SUVmax
(FDG)
Publishedstudy
Colorectal metastasisPrognostic marker10.0 Christopher C.R. et al.J
Nuc Med 2007 -(5)
Non-small lung
carcinoma
Predictor for
recurrent tumour
4.5 Shiono et al. J. of
Thoracic
Oncology.2011-(6)
Thymic tumour Predictor for
malignancy
8.5 Reimer SE et al. J Nucl
Med (1998)-(7)
Thymoma Predictor for tumour
aggressiveness
10.0 Yon et al. J Nucl
Med(2006) -(8)
Liposarcoma Predictor for disease
-free survival
3.6 Winfried B. et al.
European Journal of
Nuclear Medicine and
Molecular Imaging.
2006-(23)
Invasive ductal breast
cancer
Predictor for
progression-free
disease survival
6.6 Bong-Il S et al. Nucl
Med Mol Imaging.
(2011) –(32)
Phaechromocytoma/
Paraganglioma
recurrence
Predictor for tumour
aggressiveness
9.1 Fathinul F et al
(unpublished) –(39)

16. UTILITY OF FDG -PET AS A BIOMARKER
•LOCALISATION
•PRE-TREATMENT STAGING
•TREATMENT MONITORING
•PREDICTION OF TUMOUR
RECURRENCE/AGGRESSIVENESS
•PROGNOSTIC FACTOR

17. LYMPHOMA

18. FDG-PET ( treatment monitoring)
B-cell lymphoma (pre versus post treatment)

19. Experience of FDG-PETCT in GIT
(esophageal tumour)
n= 18
referral for tumourrestaging

22. POTENTIAL ROLE OF FDG_PET-CT IN
NEUROENDOCRINE TUMOUR

23. The critical need for Surrogate Biomarker
•Relative rare, NET cause substantial morbidity in
community
•Symptoms are innocuous
•Survival is long, suffering can be protracted
•Slow growth , low response rates using concentional
treatment
•Use of the structural imaging :
Detection of secondary deposits are poor
•NET: clonal heterogeneity-
discrimination of benign from malignant is difficult on
histology
•WHO: malignant disease is solely based on the basis of
metastasis/retrospective analysis

24. Introduction
•>13 known neuroendocrine cells that
can undergo malignant transformation
[Rindi G, Kloppel G. Endocrine tumors of the gut and
pancreas tumor biology and classification.
Neuroendocrinology 2004; 80(Suppl 1): 1215]
•Hormonal excess to constituitional
symptoms
•Peptide hormones bind to stimulatory or
inhibitory cell surface receptors (SSTR)
•NET express SSTR (subtype 2)
S
2

25. NEUROENDOCRINE
TUMOUR
•BIOLOGICAL PROPERTIES
Malignant NET
constitutes a rare
heterogenous group
of tumour
NET adrenal,
endocrine Islets
(thyroid , pancreas)
Digestive and
respiratoyr tracts
Indolent
Growth
•Well
differentiated
aggressive
•Poorly
differentiated
Malignant
potential
•De-
differentiated

26. 600×411-...progression to a higher grade of de-
differentiationand malignancy
FDG-PET: Prediction of aggressiveness

27. Imaging Biomarkers!
In this patient with metastatic NET, co-registered
image in transaxial planes demonstrate sites (cross-
hairs) of high FDG uptake on PET (left panels) lacking
in somatostatin receptor expression based on In-111
octreotide SPECT (right panels) scanning.
….unlike most tumours, no
molecular or cellular markers
can identify a PCC/PGL as
malignant. Vascular invasion
and cellular atypia, do not
definitively identify a
PCC/PGL as malignant

28. PET with 68Ga DOTA-Octreotide

29. FDG-PET: TumourLocalisation
•? Reliability of FDG-PET
–: useful marker in localising
metastatic/recurrent PCC/PGL
TimmersHJ, et al.
Superiority of fluorodeoxyglucosepositron emission tomography to other functional imaging
techniques in the evaluation of metastatic SDHB-associated pheochromocytomaand
paraganglioma. J.Clin.Oncol. 2007 Jun 1;25(16):2262-2269

31. Mean SUVmax between local control & metastasis
SUVmax:
7.78
SUVmax: 14.08

32. Factor No of Patients p
Local control
(n=9)
Metastasis
(n=14)
TumourSUVmax
<9.2
>9.2
9
0
6
8
**0.03
Tumoursize
<2.0cm
>2.0cm
9
0
9
5
0.14
Serum
catecholamine
positive
negative
2
7
12
2
0.18
Predictors for localcontrol/metastasis
** : Fischer’s exact test: significant value P<0.05

33. •The problem with molecular heterogeneity
•Tumour with indistinguishable histology
demonstrated quite different response to therapy
FDG-PET: Pre-treatment staging:

34. Chemother
apy
Radio
peptide
therapy
FDG-PET: therapeutic determination

35. Targeted Therapy
R.J. Hicks. Cancer Imaging.2010;10(1A): S83–S91.

36. Biomarkers In vitro tumour
signaling
Glut-1
Glycolytic metabolism
Ki-67
Tumour proliferation
p 53
Tumourapoptosis
CORELATION
WITH PRECLINICAL BIOMARKERS

37. After
6mo

38. FDG
ADC
HER -VE
MRS-Cho
FDG PET-MRI(ADC)-
MRS

39. Thank you

40. After 6mo
FDG; Disease predictor