Lutetium-177 (¹⁷⁷Lu) [Neurosurgery Wiki]

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====== 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.

===== Key Characteristics =====

^ Property ^ Description ^
| Half-life | ~6.7 days |
| Beta energy (Eβmax) | 497 keV |
| Gamma energy | 208 keV (11% abundance) |
| Tissue penetration | 0.2 to 2 mm (depending on tissue density) |
| Production | Produced by irradiating ytterbium-176 targets in nuclear reactors. |

===== Importance in Medicine =====

**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.

===== Example: Application in Glioblastoma =====

{{rss>https://pubmed.ncbi.nlm.nih.gov/rss/search/1DK1DQN9MQ-Aev8iI8NOE2_NmRtObC9CzCA2sqyFp7_qPebgi_/?limit=15&utm_campaign=pubmed-2&fc=20250426072733}}

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
((Ghaedian T, Alipour A, Rakhsha A, Nasrollahi H, Ghaedian M, Andalibi S, Saffarian A. Excellent Response of Glioblastoma Multiforme to [177Lu] Lu-PSMA Therapy. Clin Nucl Med. 2025 Apr 28. doi: 10.1097/RLU.0000000000005904. Epub ahead of print. PMID: 40279656.))

**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
((Kumar A, Ballal S, Yadav MP, ArunRaj ST, Haresh KP, Gupta S, Damle NA, Garg A, Tripathi M, Bal C. 177Lu-/68Ga-PSMA Theranostics in Recurrent Glioblastoma Multiforme: Proof of Concept. Clin Nucl Med. 2020 Dec;45(12):e512-e513. doi: 10.1097/RLU.0000000000003142. PMID: 32558721.)).