What is Theranostics? 

Future Directions in Theranostics

​

1. Alpha-Emitting Isotopes (example: Actinium-225) for More Potent Localized Radiation Alpha emitters like Actinium-225, Bismuth-213, and Astatine-211 are gaining momentum in theranostics due to their high linear energy transfer (LET) and short tissue penetration range (~50–100 µm). This allows them to deliver highly cytotoxic radiation specifically to cancer cells, sparing surrounding healthy tissues.

 

Advantages:

​

High potency: Alpha particles cause double-stranded DNA breaks, which are more difficult for cancer cells to repair.

Minimal collateral damage: Due to limited travel distance, alpha radiation reduces damage to nearby normal cells.

 

Applications under study:

• Prostate cancer (example: targeted alpha therapy using Actinium-225–labeled PSMA ligands).

• Leukemias and lymphomas, due to the ability of alpha particles to eradicate minimal residual disease.

• Combination with nanocarriers to improve delivery specificity and reduce systemic toxicity.

​

​

2. Combination Therapies with Immunotherapy or PARP Inhibitors
The synergy between theranostics and other targeted therapies is a promising area of development.

Theranostics + Immunotherapy:

• Radiation from theranostic agents can upregulate neoantigen presentation, enhancing immune system recognition.

• Radiation-induced immunogenic cell death may boost the efficacy of checkpoint inhibitors (example: PD-1, CTLA-4).

Trials are ongoing combining radionuclide therapy with CAR-T cells or immune checkpoint blockade in solid tumors.

Theranostics + PARP Inhibitors:

• PARP inhibitors (example: olaparib) impair DNA repair in tumors with BRCA mutations or homologous recombination deficiencies.

• Combining with radionuclide therapy exploits synthetic lethality, overwhelming the cancer cell's ability to repair radiation-induced DNA damage.

• Especially relevant in ovarian, breast, and prostate cancers.

​

​

3. Theranostics Under Development for New Tumor Types

While prostate and neuroendocrine tumors have seen the most clinical success so far, research is expanding into more challenging cancers:

a. Thyroid Cancer

Traditionally treated with radioactive iodine (I-131), now being re-explored with:

Next-gen iodine isotopes (I-124 for PET imaging).

Improved tracers for dedifferentiated thyroid cancers that lose iodine avidity.

Sodium-iodide symporter (NIS) gene therapy combined with radioiodine.

b. Breast Cancer

Development of HER2-targeted radioligands, enabling diagnosis and therapy in HER2-positive cases.

Investigational use of FAP-targeted theranostics (fibroblast activation protein), relevant for triple-negative breast cancer.

Imaging agents using 89Zr-labeled trastuzumab to map HER2 expression.

​

c. DLL3-Expressing Cancers
Delta-like ligand 3 (DLL3) is an inhibitory Notch ligand aberrantly overexpressed in several aggressive cancers, particularly small cell lung cancer (SCLC) and other neuroendocrine tumors, while having minimal expression in normal tissues. Its tumor-specific expression makes it an attractive target for novel radionuclide-based theranostics.

​

d. Glioblastoma
One of the most aggressive and therapy-resistant brain tumors.

Challenges: blood–brain barrier (BBB), heterogeneity.

Emerging approaches:

• Theranostic nanoparticles that cross the BBB.

• Targeted alpha therapy with ligands like substance P or IL-13 conjugates.

• Research into EGFRvIII or integrin αvβ3 targeting for glioblastoma imaging and treatment.

​

e. Newly emerging targets and radio isotopes

• GRPR

• FAP

• Integrin

• etc. 

​​