Development of New Radiopharmaceuticals for Targeted Radionuclide Therapy of Brain Cancer

1.Targeted Radionuclide Therapy for Brain Cancer:

• • • Targeted radionuclide therapy (TRT) is a type of radiation therapy that can be used to treat brain tumors.
    • A radioactive chemical, called a radionuclide, is attached to a molecule that binds to specific targets on cancer cells. The therapy then delivers a cytotoxic dose of radiation to the cancer cells while minimizing damage to healthy tissue.

2. Brief Overview of Brain Cancer and Current Treatment Challenges

• • • Brain cancer can be a life-threatening disease that affects the brain's vital structures.
    • Brain cancer can be primary, which starts in the brain, or secondary, which starts in another part of the body and spreads to the brain. 
    • Current Treatment Challenges
• Surgery
• Chemo therapy  
• Radiation therapy
• Targeted therapies
•  Immuno therapy

 3. Importance of Targeted Radionuclide Therapy:

• Highly specific treatment: Targets cancer cells while sparing healthy tissue
• Effective against hard-to-reach tumors: Can reach tumors deep in the brain or with limited surgical assess.
• Minimizes side effects: Reduce harm to surrounding healthy tissue and organs
• Improves quality of life: Relieves symptoms, reduces pain, and enhances daily functioning
• Potential for improved survival rates: Increases chances of long-term survival and cure
• Combination therapy: Can be used in conjunction with surgery, chemotherapy, and immunotherapy for enhanced treatment
• Personalized medicine: Allows for tailored treatment plans based on individual patient needs and tumor characteristics
• Advancements in technology: Enables precise delivery and monitoring of radiation dose
• Growing research and development: Expanding options for various types of brain cancer and other diseases. 

BACKGROUND:

1. Overview of Radiopharmaceuticals and Applications: 

• Radiopharmaceuticals are medications containing small amounts of radioactive materials, used for diagnostic, therapeutic, and research purposes.
• They offer targeted therapy, non-invasive procedures, and personalized medicine, but also pose risks of radiation exposure, regulatory challenges, and limited availability.
• Common types include Technetium-99m, Iodine-131, Lutetium-177, Fluorine-18, and Strontium-89, used for various applications such as cancer treatment, pain management, and diagnostic imaging.

2. Principle of Targeted Radionuclide Therapy:

• Targeted radionuclide therapy follows 10 key principles to effectively treat diseases like cancer while minimizing harm to healthy tissues.
• These principles include target specificity, radiation type selection, radiopharmaceutical design, optimized biodistribution, precise dosimetry, personalized medicine, combination therapy, minimizing side effects, monitoring and evaluation, and continuous research and development.
• By adhering to these guidelines, treatment can be tailored to individual patient needs, maximizing its potential benefits.

3. Current Radiopharmaceuticals Used in Brain Cancer:

•  Glioblastoma:

 Bq-BC8 (Lutetium-177 labeled peptide) and I-131-TM-601 (Iodine-131 labeled antibody)

• Malignant glioma:

 Y-90-DOTA (Yttrium-90 labeled peptide) and Lu-177-DOTATATE (Lutetium-177 labeled peptide)

•  Brain metastases: 

 Rhenium-186 (Rhenium-186 labeled liposomes) and Samarium-153 (Samarium-153 labeled liposomes)

•  Neuroblastoma: 

 I-131-MIBG (Iodine-131 labeled metaiodobenzylguanidine)

•  Medulloblastoma: 

 Y-90-DOTA (Yttrium-90 labeled peptide)

New Radiopharmaceuticals and Developement

Fig No:1

• GBR-1303 radiolabelled antibody targeting Glioblastoma.
• DOTATOCI radiolabeled peptide targeting somatostasis receptor.

• LU-177- PSMA-617: radiolabeled small molecule targeting PSMA in Brain metastasis.

Pre-Clinical Studies:

Fig No:02

Preclinical studies in new radiopharmaceuticals for targeted radionuclide therapy of brain cancer involve researching and testing new radiopharmaceuticals (RPs) that selectively target and destroy cancer cells in the brain while minimizing harm to healthy cells.

These studies aim to:

• Identify and synthesize new RPs with high affinity and selectivity for brain cancer cells.
• Evaluate their efficacy, toxicity, and pharmacokinetics in animal models.
• Optimize dosing and treatment regimens.

Clinical Trials

Fig No:03

Clinical trials for radiopharmaceuticals are conducted to establish their safety and efficacy as diagnostic or therapeutic agents.

Comparison

• To prove efficacy, radiopharmaceuticals are compared to existing agents or other relevant medicinal products and procedures. 

Phases

• Most radiopharmaceutical trials are in the early stages of development, with over 80% in Phase 1, Phase 1-2, or Phase 2. 

Radiopharmaceutical Development Initiative (RDI)

• RDI involves both early and late phases. 

Biomarkers

• Biomarkers are important for selecting treatments and evaluating the clinical performance of radiopharmaceuticals

Challenges and Future Directions: