Oncology

Role of Nuclear Medicine in Oncology

Key Applications:

• Diagnosis: Detecting cancer presence.

• Staging: Determining the extent and spread of cancer.

• Monitoring: Assessing response to treatment.

• Treatment: Guidance for targeted therapy.

Common Radiopharmaceuticals in Oncology

• Gallium-67 (Ga-67)

• Thallium-201 (Tl-201)

• Technetium-99m (Tc-99m Sestamibi, DMSA)

• Iodine-123 (I-123 MIBG)

• Indium-111 (In-111 Octreotide)

• Fluorine-18 FDG (F-18 FDG, PET Imaging)

Gallium-67 (Ga-67)

Physical Characteristics

• Production: Cyclotron (proton irradiation of enriched zinc).

• Half-Life: 78.2 hours.

• Decay Mode: Electron capture to Zn-67.

• Energy Spectrum: Gamma emissions (93, 184, 296, 388 keV).

Biological Characteristics

• Binds to plasma proteins (lactoferrin, transferrin, ferritin).

• Transferrin receptors (CD71) are increased in proliferating cells.

• Biodistribution: Liver, spleen, bone marrow, nasopharynx, thymus, salivary/lacrimal/mammary glands.

• Excretion:

  • First 24 hours: Renal (10-25%).

  • After 24 hours: Hepatobiliary and gastrointestinal.

Indications

• Cancer Types:

  • Hodgkin’s lymphoma (>90% sensitivity/specificity).

  • Non-Hodgkin’s lymphoma, melanoma, seminoma, lung, hepatocellular carcinoma, sarcomas, neuroblastoma.

• Infection & Inflammatory Disease: Acute inflammatory conditions.

Scanning Protocol

• Dose: 300–400 MBq IV.

• Preparation: Bowel prep (optional), void bladder.

• Timing: Imaging at 48-72 hours post-injection.

• Acquisition:

  • Whole Body Scan: 8 cm/min.

  • Planar Imaging: 256 × 256 matrix.

  • SPECT/CT: 64 × 64 matrix (30-40 sec/view).

False Negatives & False Positives

• False Negatives:

  • Small tumors, early-stage NHL.

  • Recent chemotherapy or MRI with gadolinium.

• False Positives:

  • Infection, inflammation, benign processes, recent surgery.

Thallium-201 (Tl-201)

Physical Characteristics

• Production: Cyclotron (proton irradiation of Tl-203).

• Half-Life: 73 hours.

• Decay: Electron capture.

• Energy Spectrum: 60-80 keV X-rays, 135 & 167 keV gamma rays.

Biological Characteristics

• Uptake Mechanism:

  • Uses Na+/K+ ATPase pump (like potassium).

  • Accumulates in viable cells but not in necrotic tissue.

• Biodistribution:

  • Initial Uptake: Cardiomyocytes, liver, lungs, kidneys.

  • Late Uptake: Brain (if BBB is disrupted), kidneys, GIT.

• Excretion: Kidney and GIT (25% in first 24 hours).

Indications

• Brain Tumors: Glioblastoma, recurrent gliomas.

• Differentiation: Malignant vs. inflammatory lesions.

• Lung, Breast, Head & Neck Cancers.

• Lymphoma (low-grade NHL).

Scanning Protocol

• Dose: 75-150 MBq.

• Acquisition:

  • Early Imaging: 15-30 min post-injection.

  • Delayed Imaging: 4-6 hours later.

  • WB Scan: 10 cm/min.

  • Planar Imaging: 512 × 512 matrix (initial), 128 × 128 matrix (delayed).

  • SPECT/CT: 20-30 sec/view.

Technetium-99m (Tc-99m) Sestamibi

Physical Characteristics

• Production: Decay of Molybdenum-99.

• Half-Life: 6 hours.

• Energy: 140 keV gamma photon.

• Lipophilic, cationic molecule.

Biological Characteristics

• Uptake Mechanism:

  • Passively diffuses across membranes.

  • Retained in mitochondria (dependent on metabolic activity).

• Biodistribution:

  • High Uptake: Myocardium, thyroid, parathyroid, salivary glands, spleen, kidneys, lungs.

• Excretion: Hepatobiliary (minor renal clearance).

Indications

• Cancer Localization & Staging:

  • Breast cancer (>80% sensitivity/specificity).

  • Parathyroid adenoma.

  • Thyroid, lung, multiple myeloma.

• Limitations:

  • High endogenous uptake in the abdomen.

  • No correlation with tumor grade.

  • Some tumors express P-gp pumps that expel sestamibi.

Scanning Protocol

• Dose: 740 MBq.

• Timing: Early (5-10 min) and late (2-4 hrs) imaging.

• Acquisition:

  • Planar Imaging: 10 min lateral/anterior views.

  • SPECT/CT: 360° rotation, 20 sec/view.

Fluorine-18 FDG (F-18 FDG) – PET Imaging

Physical Characteristics

• Half-Life: 109 minutes.

• Decay Mode: Positron emission (511 keV photons).

• Production: Cyclotron (O-18 target).

Biological Characteristics

• Uptake Mechanism:

  • Glucose analogue, taken up by glucose transporters.

  • Phosphorylated and trapped in cells.

• Biodistribution:

  • High Uptake: Brain, myocardium, liver, bone marrow.

  • Excretion: Urinary tract.

Indications

• Staging & Response Monitoring:

  • Lung, melanoma, lymphoma, sarcoma, GIT, breast, prostate, brain, cervical cancers.

• Limitations:

  • False positives in inflammation/infection.

  • False negatives in slow-growing tumors.

Scanning Protocol

• Dose: 4 MBq/kg.

• Preparation:

  • Fast 6 hours, no exercise 24 hours before.

  • Blood sugar <10 mmol/L.

• Acquisition:

  • WB imaging: 60 min post-injection.

  • SPECT/CT: 128 × 128 matrix, 20-30 sec/view.

The lecture continues with additional nuclear medicine tracers used in oncology, including Tc-99m DMSA, I-123 MIBG, In-111 Octreotide, and newer PET tracers. Here’s a continuation of the in-depth notes:

Technetium-99m (Tc-99m) Dimercaptosuccinic Acid (DMSA)

Biological Characteristics

• Valency-Dependent Behavior:

  • DMSA (III): Accumulates in the proximal renal tubule.

  • DMSA (V): Used for oncology.

• Uptake Mechanism:

  • Structural similarity with phosphate ions (PO4³⁻).

  • Acts as a phosphate transport marker via Type III NaPi co-transporters.

  • Tumor microenvironments with low pH promote higher uptake of DMSA(V).

• Biodistribution:

  • Blood pool (heart & vessels), nasal mucosa, lacrimal glands.

  • Pituitary gland, breast tissue.

• Excretion: Renal clearance.

Indications

• Medullary Thyroid Carcinoma:

  • Accounts for ~3% of all thyroid cancers.

  • Symptoms: Increased calcitonin secretion, flushing, diarrhea.

  • Common metastatic sites: Lymph nodes, bone, lung, liver.

Scanning Protocol

• Dose: 370 MBq IV.

• Timing: Whole body scan (2-3 hours post-injection).

• Imaging:

  • Planar & Whole Body Imaging: Used to assess lymph node involvement.

  • SPECT/CT: Localizes metastatic lesions.

Iodine-123 Metaiodobenzylguanidine (I-123 MIBG)

Physical Characteristics

• Half-Life: 13.1 hours.

• Decay: Electron capture to Tellurium-123.

• Energy Spectrum: 159 keV gamma photon (83% abundance).

• Production: Cyclotron (proton bombardment of Xenon-124).

Biological Characteristics

• Mechanism of Uptake:

  • Structurally similar to norepinephrine.

  • Actively transported into adrenergic nerve terminals.

• Normal Biodistribution:

  • High Uptake: Salivary glands, myocardium, lungs, liver, GI tract, bladder, brown fat.

Indications

• Tumors of Neuroendocrine Origin:

  • Pheochromocytoma.

  • Paraganglioma.

  • Neuroblastoma.

  • Carcinoid tumors.

  • Medullary Thyroid Carcinoma.

Scanning Protocol

• Dose: 400 MBq IV.

• Patient Preparation:

  • Lugol’s Iodine (1 day before & 1–2 days post-injection) to block thyroid uptake.

  • Medication Review (Certain drugs block uptake, e.g., beta-blockers, antidepressants).

• Acquisition:

  • Whole body imaging at 24, 48, and 72 hours post-injection.

  • SPECT/CT: Distinguishes soft tissue from skeletal lesions.

  • False Positives: Urinary contamination, normal adrenal uptake.

  • False Negatives: Small or necrotic tumors.

Indium-111 Octreotide (In-111 Octreoscan)

Physical Characteristics

• Half-Life: 2.8 days.

• Decay: Electron capture.

• Energy Spectrum: 171 & 245 keV gamma photons.

• Production: Cyclotron (proton irradiation of Cd-112).

Biological Characteristics

• Mechanism of Uptake:

  • Octreotide binds somatostatin receptors (SSR).

  • SSR Type 2 is overexpressed in many neuroendocrine tumors.

• Normal Biodistribution:

  • High Uptake: Liver, spleen, thyroid, pituitary, nasopharynx, urinary tract.

• Excretion: 50% via urine in 6 hours, 85% by 24 hours.

Indications

• Tumor Localization & Prognosis:

  • Carcinoid tumors.

  • Gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

  • Pituitary adenomas.

  • Small Cell Lung Carcinoma.

  • Adrenal Medullary Tumors (Pheochromocytoma, Neuroblastoma).

  • Merkel Cell Tumor.

Scanning Protocol

• Dose: 200 MBq IV.

• Patient Preparation:

  • Withdraw long-acting somatostatin therapy (if applicable) 3-4 weeks before.

  • Ensure hydration (to enhance renal clearance).

• Acquisition:

  • Imaging at 4 & 24 hours (optional 48 & 72 hours).

  • SPECT/CT: Used when lesions are visualized.

  • False Negatives: Small tumors, masking by bowel activity.

  • False Positives: Granulomatous disease, inflammation.

Fluorine-18 FDG (F-18 FDG) – PET Imaging

Concepts

• High-energy positron emitter (511 keV).

• Positron annihilation produces two 511 keV gamma photons traveling in opposite directions.

• Coincidence detection: PET scanner detects simultaneous 511 keV photons.

Biological Characteristics

• Uptake Mechanism:

  • Glucose analogue, transported into cells via GLUT transporters.

  • Phosphorylated by hexokinase, but cannot undergo glycolysis, leading to intracellular trapping.

• Biodistribution:

  • High Uptake: Brain, myocardium, liver, bone marrow.

  • Excretion: Urinary tract.

Indications

• Cancer Staging & Treatment Monitoring:

  • Melanoma, Lung Ca (SCLC & NSCLC), Breast, Lymphoma, GIT, Cervical Ca, Brain, Sarcoma, Head & Neck Ca.

• Limitations:

  • False positives: Inflammation, infection.

  • False negatives: Slow-growing tumors.

Scanning Protocol

• Dose: 4 MBq/kg.

• Patient Preparation:

  • Fast 6 hours.

  • Avoid strenuous activity for 24 hours.

  • Check diabetes status.

• Acquisition:

  • Whole body (WB) for melanoma.

  • Vertex to mid-thigh for most cancers.

  • SPECT/CT: 128 × 128 matrix, 20-30 sec/view.

Emerging PET Tracers

Alternative Tracers for Specific Tumors

Conclusion

Key Takeaways

• Ga-67: Used for lymphoma & infections.

• Tl-201: Brain tumors & lymphoma.

• Tc-99m Sestamibi: Breast cancer & multiple myeloma.

• I-123 MIBG: Neuroendocrine tumors.

• In-111 Octreotide: Somatostatin receptor imaging.

• F-18 FDG PET: Gold standard for metabolic imaging in oncology.