1. Nuclear medicine involves using radioactive substances to diagnose and treat disease. Positron emission tomography (PET) uses radiotracers like fluorodeoxyglucose (FDG) to detect cancer cells and investigate their metabolism. 2. Cancer cells have altered metabolism and proliferation compared to normal cells. The Warburg effect shows they rely more on glycolysis than oxidative phosphorylation. This increased glycolysis can be detected on PET scans using FDG. 3. PET scans have many clinical applications, including cancer staging, detecting metastases, assessing treatment response, and distinguishing tumor recurrence from treatment effects. They provide functional information to guide diagnosis and management.

1. NUCLEAR IMGING IN
CANCER

2. NUCLEAR MEDICINE
• Medical specialty involving the application
of radioactive substances in the diagnosis
and treatment of disease
• Physiological function investigated
• Diagnostic
– 2D: Scintigraphy
– 3D: SPECT
– Positron emission tomography (PET)
– Hybrid scanning techniques

4. Single-photon emission computed tomography

5. • Radiotracers
– Isotopes + compounds used by the body
– Fludeoxyglucose (18F)
– Fluorine-18 - hydroxyl group at the 2' position of
glucose molecule
– Bombardment of neon-20 with deuterons
– Proton bombardment of 18
O-enriched water
– Knockout reaction in 18
O
– Carrier-free dissolved 18F-fluoride (18
F−
)
– 109.8 minute half-life of 18F
– Eluted with an acetonitrile solution of 2,2,2-cryptand
and potassium carbonate

6. – Cryptand to sequester the potassium ions avoids ion-
pairing between free potassium and fluoride ions
– Treated with a protected mannose triflate

10. PET SCAN

14. • Cancer cells have a characteristic altered intermediary
metabolism and increased proliferation
• Requires nutrients and basic substrates as building
blocks for proteins, DNA and RNA, lipids, and other
macromolecules

15. • Warburg Effect
– Cancer cells - high rate of glycolysis followed
by lactic acid fermentation in the cytosol
– Normal cells- low rate of glycolysis followed
by oxidation of pyruvate in mitochondria
– Glycolytic rates up to 200 times higher
– Correlation of FDG uptake and biologic
aggressiveness

17. • Cellular Proliferation and Apoptosis
– DNA - thymidine - l8F-3' deoxy-3'-flurothymidine
(FLT)
– Correlation between tissue markers of proliferation
and the intensity of FLT uptake in vitro and in vivo
– Correlates well with the expression of ki-67
– Early changes in FLT uptake may be a marker of
effective treatment in patients undergoing
chemotherapy
– FLT is not an agent for cancer detection, but rather
for measuring proliferation and treatment response

19. • Amino Acid Transport
– L-type amino acid transport up-regulated
– Reported for brain and prostate cancer
– 18F-fluorocyclobutane- 1 -carboxylic acid
(FACBC)
– Fluoroethyltyrosine (FET )

20. • Androgen and Estrogen
Receptor Expression
– 18F-estradio - breast
– l8F-fluoro-
dihydrotestosterone
(FDHT) - prostate

21. • Sodium Iodide Symporter
– 124
I - determine the dose and dose distribution
for subsequent treatment with the beta emitter
131
I in thyroid cancer

22. • Imaging the Human Epidermal Growth Factor
Receptor 2 Oncogene
– 68
G-labeled trastuzumab antibody fragment
– Level of binding is proportional to the level of receptor
expression
– Receptor number can be quantified
– Determine the effectiveness of drug response more
rapidly

23. • Gene Expression Imaging
– Herpes simplex thymidine kinase (HS V-TK)
gene
– Radiotracer 124I-FIAU ( 1 - ( 2 ' deoxy- 2 '
-fluoro- 3-D - arabinofuranosyl-5 -iodouracil )
– Monitor gene therapy or therapy with stem
cells or immunocompetent cells

24. • Hypoxia
– Imaged with labeled nitroimidazoles , for e x
a m p l e ,
– 1 8F-fluoromisonidazole (FMIS0 )
– 18F-FAZA ( 1 8F-
fluroazomycinarabinoside )
– Guiding the use of radiation sensitizers in
patients with hypoxic tumors or
– Guiding radiation dose boost to hypoxic
subvolumes

25. • Positron-labeled antibodies and antibody
fragments
• 1241-labeled cG250 for renal clear cell
carcinoma
• Recognizes carbonic anhydrase-IX
• Expressed antigen on clear cell renal cell
carcinoma

26. CLINICAL APPLICATIONS
• Distant metastases are detected in 10 %
to 20 % of cases with locally advanced
disease
• Use for radiotherapy planning
– Improves the staging accuracy
– Improves interobserver agreement
– Distinguish active disease from benign
structural abnormalities

27. • Cancer staging
– Detection of small volume disease in lymph
nodes and distance site

28. • Detectability of a small lesion depend on
– ( 1 ) the volume of metabolically active
disease
– ( 2 ) the intensity of radiotracer uptake in this
volume,
– ( 3 ) the resolution limits of the PET camera
– ( 4) background activity in normal tissues
and blood pool,
– ( 5 ) the degree of lesion motion during the
image acquisition.

29. • Assessing the response to neoadj uvant
regimens
– Distinguish between metabolic responders and
nonresponders
– Correlate with disease-free survival
– SUV change greater than 20 % is considered
significant
– at least 6 to 8 weeks when chemotherapy used
– 10 to 12 weeks when combined chemoradiotherapy
was used

30. • Metabolic flare
– Early during hormonal therapy, an
– Increase in SUV or the appearance of new
spots of FD G uptake in the skeleton
– Metabolic flare on PET herald a future
response
– Indicators of a good prognosis

31. • False negetive
– Low glucose metabolism
– Lower expression of GLUT, a
– High rate of FDG dephosphorylation -
hepatocellular carcinoma
– Histologic composition of the lesion
• Little solid tissue in a true bronchoalveolar
carcinoma;
• Diffuse, nonmass-forming growth pattern in
invasive lobular breast cancer;
• Predominantly cystic mucinous tumors, including
some pancreatic and ovarian primaries

32. • False-positive findings
– Brown adipose tissue is a frequent normal variant
– Granulomatous diseases or reactions ( e . g . ,
sarcoidosis; talc pleurodesis )
– Benign tumors ( e . g . , paragangliomas,
meningiomas, many benign bone lesions such as
eosinophilic granuloma, nonossifying fibroma,
fibrous dysplasia, Paget's disease )
– Infection (which can be used clinically for diagnosis
ofpatients with fever of unknown origin )

33. • Brain
– To differentiate between tumor recurrence and
radiation necrosis in patients treated previously with
cranial irradiation.
– Identifying the grade of malignancy where there is
uncertainty on anatomical imaging and functional
assessment would assist biopsy
– Assessment of suspected high grade
transformation in low grade glioma.
– Differentiation of cerebral tumor from atypical
infection in immunocompromised patients with
indeterminate lesions on MR/CT

34. • Head and neck tumors
– Staging of patients where staging is difficult clinically or where
there is uncertainty on other imaging or equivocal findings that
would preclude radical treatment
– Staging or restaging of patients with a high risk of disseminated
disease such as advanced loco regional disease and primary
sites with a high propensity for disseminated disease such as
nasopharyngeal cancer.
– To identify the primary site in patients presenting with metastatic
carcinoma in cervical lymph nodes, with no primary site
identified on other imaging.
– Response assessment 3-6 months post chemoradiotherapy in
patients with residual masses following treatment.
– To differentiate between radiation induced edematous changes
versus active tumor tissue.
– To rule out metastatic disease in locally advanced cancer before
major operative procedure

35. • Lymphoma
– Staging of patients with Hodgkin's disease (HD) and Non Hodgkin's
lymphoma (NHL)
– Baseline for comparison with treatment response scan.
– Interim and end of treatment response assessment of patients
withHDand aggressive NHL.
– Evaluation of suspected relapse for FDG avid lymphomas in
symptomatic patient.
– Staging of suspected post transplant lymphoproliferative disorder
(PTLD).
– Prior to bone marrow transplant to assess volume of disease and
suitability for transplant
– To determine extent and identify a suitable biopsy site in patients
with low grade lymphomas in whom there is suspected high grade
transformation.

36. • Lung carcinoma
– Staging of patients considered for radical treatment of non-small
cell lung cancer especially mediastinal nodes <1 cm on CT or
mediastinal nodes between 1–2 cm on CT or equivocal lesions
that might represent metastases such as adrenal enlargement.
– Characterization of a solitary pulmonary nodule
– Especially in the case of failed biopsy, a technically difficult
biopsy or where there is a significant risk ofa pneumothorax in
patients with medical co morbidities
– Assessment of suspected disease recurrence
– To differentiate between treatment effects and recurrent cancer
– Staging of patients with small cell lung cancer with limited
disease on CT being considered for radical therapy.
– Pleural malignancy
– To guide biopsy in patients with suspected pleural malignancy
– To exclude extra-thoracic disease in proven mesothelioma in
patients considered for multimodality treatment including radical
surgery/decortication.

37. • Breast carcinoma
– Assessment of multi focal disease or suspected
recurrence in breast cancer.
– Differentiation of treatment induced brachial
plexopathy from tumour infiltration in symptomatic
patients with an equivocal or normal MR.
– Assessment of extent of disease in selecte patients
with disseminated breast cancer before therapy.
– Assessment of response to chemotherapy in
patients whose disease is not well demonstrated
using other techniques; for example,
bonemetastases

38. • Hepatopancreaticobiliary cancers
– Staging of potentially operable primary
hepatobiliary or pancreatic malignancy
(cholangiocarcinoma, gallbladder carcinoma or
hepatocellular carcinoma) where cross sectional
imaging is equivocal for metastatic disease,who are
fit for resection and a positive PET-CT would lead
to a decision not to operate.
– Suspected recurrence of hepato-pancreaticobiliary
cancer in selected patients, where other imaging is
equivocal or negative

39. • Colorectal carcinoma
– Staging of patients with synchronous metastases at
presentation suitable for resection or patients with
equivocal findings on other imaging; for example,
pulmonary or liver lesions
– Restaging of patients with recurrence being
considered for radical treatment and/or
metastatectomy
– Detection of recurrence in patients with rising
tumour markers and/or clinical suspicion of
recurrence
– Evaluation of indeterminate presacral masses post
treatment.

40. • Thymic carcinoma
– Staging of patients considered for surgical
resection
– Assessment of indeterminate thymic lesions if
being considered for radical treatment

41. • Oesophagogastric carcinoma
– Staging/restaging of patients with
oesophageal or oesophago gastric
carcinoma, suitable for radical treatment,
including patients who have received neo
adjuvant treatment.
– Evaluation of suspected recurrence of
oesophagastric tumours when other imaging
is negative or equivocal

42. • Gastrointestinal stromal tumours
– Staging prior to treatment in patients who are likely to
require systemic therapy
– Response assessment to systemic therapy
• Kidney and ureter
– Assessment of metastatic renal and ureteric carcinoma in
difficult management situations or when standard imaging is
inconclusive
– Assessment of renal carcinoma at staging in selected cases
with equivocal findings on other imaging (recognizing that
~50% of renal cell carcinoma may not be FDG avid and that
the tracer is excreted into the urinary tract)

43. • Gynaecological malignancy
– Staging or restaging of patients with uterine
carcinoma (cervix/endometrium)considered for
exenterative surgery
– Staging of patients with cervical cancer suspected
of having locally advanced disease with suspicious
findings such as abnormal pelvic nodes onMRor at
high risk of paraaortic nodal or distant metastatic
disease.
– Suspected recurrence of endometrial and/or
cervical carcinoma when other imaging is
inconclusive

44. • Myeloma
– Assessment of patients with apparently solitary
plasmacytoma or patients with ambiguous lytic lesions on
skeletal survey.
– Suspected relapse in patients with non-secretory myeloma or
predominantly extramedullary disease.
• Skin tumours
– Staging and assessment for distant disease in
patients with melanoma when radical dissection is
contemplated (nodal or metastatic disease).
– To exclude primary malignancy where
dermatomyositis is suspected to represent
paraneoplastic manifestation.

45. • Musculoskeletal tumours
– Assessment o f suspected malignant transformation within
plexiform neurofibromas in patient with neurofibromatosis type 1
– Staging of high grade sarcomas, unless already proven to have
metastatic disease, especially
– Ewing's sarcoma, rhabdomyosarcoma, leiomyosarcoma,
osteosarcoma, malignant fibrous histiocytoma, synovial sarcoma
and myxoid liposarcoma.
– Preamputation in the setting of a high grade sarcoma where the
detection of distant disease will alter the surgical management
– To stage patients with metastatic sarcoma considered for liver or
lung metastatectomy where anatomical imaging has not
identified any extra thoracic or extra hepatic disease which
would preclude surgery
– Response assessment in high grade sarcomas

46. • Paraneoplastic syndromes
– To detect an occult primary tumour in
selected patients with non metastatic
manifestations of neoplastic disease when
other imaging is negative or equivocal
• Carcinoma of unknown primary
– Detection of the primary site when imaging
and histopathology has failed to show a
primary site, where the site of tumor will
influence choice of chemotherapy.

47. • Neuroendocrine tumours
– Staging or restaging of selected patients with poorly
differentiated neuroendocrine tumours prior to
treatment with negative or normal
metaiodobenzylguanidine (MIBG) and octreotide
scans.
– Assessment of possible multifocal disease in
patients with paraganglioma considered for surgery
– Staging and response assessment of
osteosarcoma and Ewing's sarcoma in patients with
negative bone scintigraphy

49. • side effect
• effective radiation dose of 14 mSv