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The 2025 Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting |
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| How About Actinium-225? |
| Machaba Michael Sathekge, MD, PhD |
| Machaba Sathekge presented a compelling case for Actinium-225 (²²⁵Ac) as a potent alpha-emitter in PSMA-targeted radioligand therapy for advanced prostate cancer. With a rapidly expanding clinical footprint and strong survival outcomes, ²²⁵Ac offers high-energy, short-range tumor killing while minimizing collateral damage—though challenges like daughter nuclide redistribution and hematologic toxicity remain critical hurdles. |
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| How About Lead-212? |
| David A. Pattison, MBBS, MPH, FRACP |
| David Pattison highlights Lead-212 (²¹²Pb) as a promising alpha-emitter for PSMA-targeted radioligand therapy in prostate cancer, offering high cytotoxicity, favorable imaging capabilities, and a short half-life for improved safety. Early-phase trials like TheraPb show encouraging anti-tumor activity and manageable toxicity, with one patient experiencing a 99% PSA drop and tumor shrinkage. Its molecular effects—including DNA damage, bystander killing, and immune activation—may enable potent, durable responses in mCRPC. |
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| How About Astatine-211? |
| Tadashi Watabe, MD, PhD |
| Tadashi Watabe presents on Astatine-211 (²¹¹At) as a promising alpha-emitter for PSMA-targeted radioligand therapy in advanced prostate cancer. With a short half-life, high tumor specificity, and favorable safety profile—particularly with [²¹¹At]PSMA-5—early preclinical and first-in-human data show potent tumor suppression and minimal off-target toxicity. A phase I trial is currently underway to further evaluate safety and efficacy in mCRPC patients. |
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| How About Terbium-161? |
| James Buteau, MD, FRACP, FRCPC |
| At SNMMI 2025, Dr. James Buteau presents promising early data on Terbium-161 (¹⁶¹Tb) for PSMA-targeted therapy in mCRPC. Compared to ¹⁷⁷Lu, ¹⁶¹Tb emits additional Auger and conversion electrons, delivering higher radiation doses to micrometastases. In the first-in-human VIOLET trial, ¹⁶¹Tb-PSMA-I&T demonstrated strong PSA responses (PSA90: 40%), a median rPFS of 11 months, and no dose-limiting toxicities—highlighting its potential as a next-generation radioligand therapy. |
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| A Combination of a CD46-Targeted Antibody-Drug Conjugate and a Radioimmunotherapy Agent for the Treatment of Prostate Cancer
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| Anil Parsram Bidkar, PhD
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| Anil Bidkar presents promising preclinical data on CD46-targeted therapies for prostate cancer, highlighting the synergy between antibody-drug conjugates (MMAE) and CD46-directed alpha therapy with ²²⁵Ac. In mouse models, the combination dramatically reduced tumor volume and extended survival, while dual-labeled constructs (MMAE + ²²⁵Ac) showed enhanced tumor killing. These results position CD46 as a powerful alternative target, especially for PSMA-negative or lineage-plastic mCRPC.
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| STARLiT: Stereotactic Body Radiotherapy and 177Lu PSMA-617 in Locally Advanced Prostate Cancer |
| Angela Jia, MD, PhD |
| Angela Jia presented early data on the STARLiT trial, evaluating SBRT + ¹⁷⁷Lu-PSMA-617 in locally advanced, high-risk prostate cancer—a non-hormonal alternative to long-term ADT. The trial aims to improve outcomes while reducing cardiovascular and quality-of-life burdens tied to androgen deprivation, addressing key questions about optimal dosing, synergy, and biomarkers. |
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| First-in-Human Results of Terbium-161 [161Tb]Tb-PSMA-I&T Radioligand Treatment in Patients with Metastatic Castration-Resistant Prostate Cancer (VIOLET): A Single-Centre, Single-Arm, Phase I/II Study |
| James Buteau, MD, FRACP, FRCPC |
| James Buteau presented early results from the VIOLET trial, the first-in-human study of [¹⁶¹Tb]Tb-PSMA-I&T in mCRPC. The therapy demonstrated a favorable safety profile—only 7% experienced grade 3–4 adverse events—and early signs of efficacy, with 70% PSA50 and 40% PSA90 response rates, and median rPFS of 11.1 months. These findings support further study of ¹⁶¹Tb as a potentially more potent alternative to ¹⁷⁷Lu due to its added Auger electron emission. |
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| Clinical Utility of Post-Therapy SPECT/CT after the 1st Cycle of 177Lu-PSMA-617 Therapy in Detecting Interim Disease Progression Compared to Pre-Therapy PSMA PET/CT |
| Ashwin Singh Parihar, MD |
| Ashwin Parihar presented a study showing that 38% of patients had new or enlarging lesions on SPECT/CT following the 1st cycle of ¹⁷⁷Lu-PSMA-617, despite reassuring baseline PSMA PET/CT. Discordance was strongly linked to longer intervals between imaging and treatment, emphasizing that post-therapy SPECT/CT offers vital early insights and may better guide ongoing management. |
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