Lutetium-177 (¹⁷⁷Lu)

Lutetium-177 is a radioactive isotope of the element lutetium, widely used in theranostics (both therapy and diagnostics).

It emits:

• Beta particles (β⁻): Medium-energy electrons that travel a few millimeters in tissue, causing localized damage (useful for targeted therapy).
• Gamma photons: Allow imaging with scintigraphy (e.g., SPECT scans) to monitor the treatment distribution.

¹⁷⁷Lu is crucial for:

• Targeted radiotherapy: Attached to ligands that seek out specific cancer cells.
• Precision therapy: Short beta range minimizes damage to healthy tissues.
• Theranostics: Simultaneous imaging and treatment.

Current clinical uses:

• Prostate cancer (¹⁷⁷Lu-PSMA-617 therapy).
• Neuroendocrine tumors (¹⁷⁷Lu-DOTATATE therapy).

Emerging research:

• Applications in glioblastoma, breast cancer, and renal cancer where PSMA or similar targets are expressed.

• Comparative evaluation of radiolabeled bombesin analogs [(177)Lu]Lu-AMBA and [(177)Lu]Lu-RM2 for targeting GRPR in glioblastoma model
• Prostate-Specific Membrane Antigen Radioligand Therapy in Non-Prostate Cancers: Where Do We Stand?
• First clinical experience with fractionated intracavitary radioimmunotherapy using [(177)Lu]Lu-6A10-Fab fragments in patients with glioblastoma: a pilot study
• PSMA-targeted therapy for non-prostate cancers
• Short-Interval, Low-Dose [ 177 Lu]Lu-Prostate-Specific Membrane Antigen in the Treatment of Refractory Glioblastoma
• Novel NK1R-Targeted (68)Ga-/(177)Lu-Radioconjugates with Potential Application against Glioblastoma Multiforme: Preliminary Exploration of Structure-Activity Relationships
• Graphene: Insights on Biological, Radiochemical and Ecotoxicological Aspects
• Theranostics of Metastatic Prostate Cancer Applying ⁶⁴Cu/¹⁸F/⁶⁸Ga PSMA PET-CT and ¹⁷⁷Lu Radiopharmaceuticals

Recent studies suggest PSMA is expressed not directly on GBM tumor cells, but on tumor-associated endothelial cells.

¹⁷⁷Lu-PSMA-617 therapy might:

• Damage tumor vasculature, starving the tumor.
• Bypass blood-brain barrier defects present in GBM.

Challenges:

• Variable PSMA expression.
• Need for controlled clinical trials.
• Safety concerns regarding radiation to normal brain tissue.

Case Report: A 42-year-old man with refractory GBM showed an excellent response to six doses of ¹⁷⁷Lu-PSMA-617 (100-150 mCi every 4–5 weeks), confirmed by MRI and ⁹⁹mTc-HYNIC-PSMA-11 scintigraphy ¹⁾

Future directions:

• Larger trials.
• Better patient selection.
• Combination therapies.

A 37-year-old man, treated case of left temporal glioblastoma, presented with headache, seizures, and progressive right-sided weakness with MRI evidence of recurrence. Exploratory Ga-PSMA PET/CT demonstrated PSMA expression in the recurrent lesion; it was decided to treat this patient with Lu-PSMA-617. After 3 cycles of Lu-PSMA-617, Ga-PSMA PET/CT showed significant reduction in PSMA uptake and regression in size of lesion on MRI with improvement in patient's symptoms and performance status. Lu-/Ga-PSMA theranostics has potential in patients with recurrent glioblastoma when other therapeutic options are not feasible ²⁾.