(UroToday.com) The 2025 SNMMI annual meeting featured a bladder cancer and dosimetry session and a presentation by Dr. Elisabetta Perrone discussing the tolerability and efficacy of intravesical RadioMolecularIncubator Theranostics with 177Lu-CXCR4 and 177Lu-3BP-3940 in high-grade muscle invasive bladder cancer. Bladder cancer is among the most prevalent malignancies of the urinary tract, imposing high economic burden and leaving many clinical needs unmet. In patients who are unable to undergo or refuse radical cystectomy or neoadjuvant chemotherapy, or among those that progress after neoadjuvant chemotherapy, an innovative local radioligand therapy may provide a promising alternative. Radioligand therapy exploits the overexpression of targeting molecules such as CXCR4 or FAP in the tumor, particularly in neoadjuvant chemotherapy resistant bladder cancers. Dr. Perrone and colleagues assessed the safety and efficacy of intravesical administration of 177Lu-CXCR4 or 177Lu-3BP-3940, a FAP binding peptide, in four muscle invasive bladder cancer patients.
These four patients were selected for intravesical radioligand therapy (RadioMolecularIncubator) based on immunohistochemical CXCR4 or FAP expression in tumor samples obtained via TURBT and complementary PET/CT. Depending on their molecular profile, they received either 177Lu-CXCR4 or 177Lu-3BP-3940 locally delivered via a urethral catheter. The radiotherapeutic was retained in the bladder for 60-90 minutes, with subsequent intravesical flushing (100 ml NaCl) and forced diuresis (1000 ml saline solution). Two 177Lu-3BP-3940 local radioligand therapy treatments were accompanied by 177Lu-3BP-3940 intravenous administration to address systemic disease. The investigators assessed safety based on acute and long-term toxicity and molecular imaging response according to Theranostic Response Criteria In Solid Tumors (THERCIST) on restaging PET/CT:
A 67-year-old male patient with muscle invasive bladder cancer and pelvic bone erosion, progressing after neoadjuvant chemotherapy, underwent two cycles of intravesical instillations of 177Lu-3BP-3940 (3.7 and 2.9 GBq), the second with a concurrent systemic administration of 177Lu-3BP-3940 (3.9 GBq) and pembrolizumab as radiosensitizer (200 mg). This patient had severe pelvic bone pain occurred during the night, managed with opioids. He achieved partial remission (PET/CT 7 months later) and disease-free survival of 22 months (he had surgery for bladder-intestinal fistula, but with confirmed absence of residual tumor):
An 84-year-old female patient with recurrence of muscle invasive bladder cancer 16 years after initial chemotherapy presented with trifocal uptake in the bladder wall at 68Ga-3BP-3940 PET/CT. She received two 177Lu-3BP-3940 intravesical instillations (5.4 and 4.8 GBq), the second paired with a systemic dose (7 GBq), achieving nearly complete remission two months later. No long-term hematological, renal, or hepatic toxicity was reported:
A 67-year-old patient was treated with 177Lu-CXCR4 intravesical instillation (4 GBq), experiencing a painless self-limiting hematuria, and subsequently treated with chemotherapy (3 cycles MVAC). Restaging 68Ga-CXCR4 PET/CT one month later revealed complete remission, confirmed by repeated TURBT two months later:
Finally, a 79-year-old patient with muscle invasive bladder cancer with plasmacytoid differentiation faced complications during cystectomy due to sigmoid adhesion and abdominal muscle infiltration. 68Ga-CXCR4 PET/CT showed intense uptake in the entire bladder wall, abdominal muscle, and sigmoid colon. He received 177Lu-CXCR4 intravesical instillation (3.6 GBq), accompanied by hematuria. Restaging is currently planned:
Dr. Perrone concluded her presentation discussing the tolerability and efficacy of intravesical RadioMolecularIncubator Theranostics with 177Lu-CXCR4 and 177Lu-3BP-3940 in high-grade muscle invasive bladder cancer with the following take home points:
- Targeting FAP and CXCR4 (molecular profiling) is a promising treatment option for muscle invasive bladder cancer for patients unwilling or unable to undergo radical cystectomy or neoadjuvant chemotherapy, or those that are progressing under neoadjuvant chemotherapy
- Intravesical radioligand therapy (RadioMolecularIncubator) has high concentrations of radiopharmaceuticals directly to the tumor, with increased local efficacy, and decreased systemic side effects
- The combined intravesical + systemic administration of radiolabeled molecules against FAP or CXCR4 extends the therapeutic possibilities (addressing also lymph node metastasis and distant metastases)
- Intensified treatment may include intravesical radioligand therapy + immunotherapy
- Intravesical radioligand therapy has excellent tolerability (no relevant adverse events) and encouraging efficacy and survival results
- This treatment has a favorable impact on patient’s quality of life, preserving the bladder and avoiding surgery and post-surgical complications, as well as reducing chemotherapy-related adverse events
- Prospective clinical trials to further assess safety, efficacy, and survival of intravesical radioligand therapy in patients with high risk muscle invasive bladder cancer are needed
Presented by: Elisabetta Perrone, MD, Institute of Nuclear Medicine, Università Cattolica del Sacro Cuore, Rome, Italy
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2025 Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting, New Orleans, LA, June 21st – 24th, 2025