Theranostics in Cancer
THERANOSTICS IN CANCER TREATMENT
Course Information
Course Title: Theranostics in Cancer Treatment
Theme: Theranostics - Now and the Future
Lecturer: ally-Ann Cryan
Date: 05 Nov 2025
Institution: RCSI Royal College of Surgeons in Ireland
LEARNING OUTCOMES
Outline what is meant by theranostics in the context of cancer therapy:
Understand the fusion of diagnostic methods with therapeutic agents for enhanced cancer treatment.
Discuss the importance of precision medicine for enhanced treatment outcomes:
Emphasize tailor-made treatments based on individual genetic and molecular profiles.
Provide examples of molecularly targeted treatments for cancer:
Review specific therapeutic modalities focusing on molecular targets unique to certain cancers.
WHAT IS THERANOSTICS
Definition:
“Theranostics” is the combination of diagnosing and therapeutic processes to treat diseases, particularly cancers.
The term is a blend of Therapeutic and Diagnostic.
Significance:
Theranostics aids in identifying the most effective treatment protocols by combining diagnosis with personalized therapy.
THERANOSTICS: THE POSSIBLE SCENARIOS
Therapeutic followed by Diagnostic:
Example: A drug that demonstrates efficacy in treatment, but only for specific patient subsets; thus, new diagnostic methods identify suitable patients.
Diagnostic followed by Therapeutic:
A diagnostic test that can distinguish patient types or disease stages, allowing more accurate therapy selection.
Co-development:
Example: Herceptin and HerceptTest for breast cancer, where the therapy and diagnostic tools were developed and approved simultaneously.
THERAPEUTIC FOLLOWING BY DIAGNOSTIC
Example of Biomarkers:
Oncotype DX 21 genomic test:
One of the first validated molecular tests for providing a risk stratification model predicting benefits of adjuvant chemotherapy for breast cancer patients.
DIAGNOSTIC FOLLOWED BY THERAPEUTIC
Use of Tumor-Specific Ligand:
A ligand that can be employed for both imaging and therapeutic applications, depending on the chosen radioisotope.
Example: Use of [68Gallium/177Lutetium] PSMA (prostate-specific membrane antigen):
PET imaging is performed before and after treatment in prostate cancer patients.
Therapeutic radiopharmaceuticals labeled with β-emitting radionuclides are utilized to damage tumor cells through energy loss over tissue traversal.
Positron Emission Tomography (PET):
A nuclear imaging technique enabling radionuclide visualization and quantified assessment in non-toxic amounts.
CO-DEVELOPMENT: COMPANION DIAGNOSTICS
Herceptin® (Trastuzumab):
A monoclonal antibody used for HER2-positive breast cancer treatment.
FDA Approval:
First approval received in 1998, with the HER2 diagnostic test (HercepTest) simultaneously authorized for assessing HER2 protein levels.
Clinical Relevance:
Approximately 20-25% of breast cancer patients overexpress HER2, which correlates with a more aggressive disease form.
These cancers may show less responsiveness to standard treatment approaches including selected chemotherapy regimens and hormone therapies.
The diagnostic test detects elevated HER2 levels in tumors and excess copies of the HER2 gene, indicating potential efficacy of Herceptin.
EARLY THERANOSTIC DEVELOPMENT
Historical Efforts (1930s):
Initial studies on phosphorous-32, a radioactive isotope for bone tumor treatment, were not commercially developed.
Advancements in Radiochemistry:
Synthetic approaches led to the creation of iodine-131, generated in cyclotrons at MIT.
Early assessments in rabbits, progressing to human trials for thyroid cancer and hyperthyroid conditions.
Function of Iodine-131:
Iodine uptake by the thyroid gland results in imaging and selective tissue destruction, achieving a 90% cure rate for patients.
THERANOSTICS IN THE CLINIC
Current Approvals:
Theranostics are approved for use in conditions such as thyroid disease, neuroendocrine tumors, and prostate cancer using nuclear medicine protocols.
Theranostic Approach:
Basis involves a ligand specifically binding to target cells and being chemically linked with a radioisotope for diagnostic or therapeutic applications.
Employing the same ligand with different radionuclides enhances targeting precision and minimizes side effects.
NUCLEAR MEDICINE
Radionuclide Therapy Definition:
Application of an unstable nuclide with a targeting vector to selectively deliver therapeutic radiation to malignant cells.
Theranostic Framework:
Involves using a duo of radiopharmaceuticals for imaging and treatment, which demands careful selection of radionuclides, as most radiopharmaceuticals lack the proper emission characteristics for both purposes.
NUCLEAR THERANOSTIC AGENTS
Comprehensive review citations:
Shrivastava, S., et al (2019) explores targeted diagnosis and therapy approaches.
THERANOSTICS IN THE CLINIC: COMPONENTS
Theranostics consist of:
A ligand to target diseased cells.
A radionuclide for therapy or imaging.
A linker to attach the ligand to the radionuclide.
Examples of Agents:
Radionuclide
Linker
Ligand
Indication
Status
Iodine-131
None
None
Imaging and treatment of thyroid cancer
Approved
Iodine-123
None
Octreotide
Imaging of neuroendocrine tumors
Approved
Lutetium-177
DOTA
Octreotide
Treatment of neuroendocrine tumors
Approved (Sandoz, Erasmus Medical Center)
Gallium-68
Lutetium-177
DOTA
Diagnosis of metastatic castration-resistant prostate cancer
Phase 3 clinical trial
THERANOSTICS – NEUROENDOCRINE TUMORS
Lutathera®:
Utilized in treating unresectable or metastatic progressive somatostatin receptor-positive neuroendocrine tumors (GEP-NETs) in adults.
FDA approval in 2018, EMA approval in 2017.
Mechanism: Combines a radionuclide with a peptide binding to specific receptors on tumor cells while sparing normal tissue.
Diagnostic Radionuclide: [68Ga]-DOTA-TATE; Therapeutic Radionuclide: [177Lu]Lu-DOTA-TATE.
THERANOSTICS – PROSTATE CANCER
[177Lu]Lu-PSMA-617 (Pluvicto®):
FDA approved in 2022.
Targets prostate-specific membrane antigen, overexpressed in prostate tumor tissues but minimally expressed in normal tissues.
Established PSMA targeting agents for imaging and therapeutic applications.
Purpose of PSMA-617:
Identified as a treatment option for patients with advanced prostate cancer resistant to hormone deprivation therapy.
THERANOSTIC NANOPARTICLES: EXAMPLES IN CANCER
Factors Influencing Cancer Targeting:
Biodistribution of Drug: Role of the reticuloendothelial system (RES) and its clearance mechanisms.
Tumor Microenvironment Characteristics:
Overexpression of receptors and enzymes.
Presence of a hypoxic core and acidic environment due to metabolic activities.
Formation of aberrant vascular networks.
Existence of leaky vessels with inadequate lymphatic drainage.
Enhanced Penetration & Retention (EPR Effect): Heightened targeting ability resulting from unique tumor characteristics.
EXAMPLES OF NANOTHERANOSTICS IN CANCER
Gold Nanoparticles:
Therapeutic Agent: Doxorubicin conjugated to gold nanoparticles (AuNP), used for in vivo imaging with fluorescence.
Targeting Moiety: Peptide substrate CPLGLAGG informed by Chen et al. (2013).
Neural Cell Adhesion Molecule (NCAM)-targeted liposomes:
Nanocarrier: Liposomes laden with doxorubicin.
Diagnostic Agent: Gadolinium derivative for MRI visualization, referenced by Grange et al. (2010).
Dendrimer Entrapped Gold Nanoparticles:
Nanocarrier: Dendrimer formulation facilitating imaging (CT) and apoptosis in cancer cells by targeting αvβ3 integrin.
CONCLUSION
The exploration of theranostic strategies showcases the transition towards more personalized cancer management approaches leveraging diagnostic and therapeutic synergies.
ADITIONAL CLASS INFORMATION
Next Session: Introduction to Nanoparticle Characterisation on November 18th, 2025.
Location: Dispensing Lab (Bring laptop for interactive component).