Key Points from Dr. Calais's Presentation:

Dr. Calais discussed cancer molecular imaging, nanotechnology, and theranostics, with a focus on PSMA (Prostate Specific Membrane Antigen) targeted imaging and therapy.

He explained how PET/CT imaging can be used for prostate cancer staging and restaging at different stages of the disease journey - from initial diagnosis to assess if cancer has spread beyond the prostate, during recurrence to locate where cancer has returned, and in advanced disease to evaluate therapy response and plan treatments.

PSMA PET imaging targets a cell surface protein expression and has been shown to be superior to other imaging modalities like CT, bone scan, and other PET techniques in terms of sensitivity and diagnostic performance.

The first PSMA agent was approved in December 2020, and now multiple commercial options are available from various vendors in the US and Europe.

Dr. Calais noted that the different PSMA tracers behave similarly, with only minor differences, and are generally considered clinically equivalent.

A limitation of PSMA PET is sensitivity - it still misses about 60% of micrometastases in pelvic lymph nodes that are too small to detect but can be seen under a microscope after surgery.

Most prostate cancer cells express PSMA at high intensity, but about 10-15% do not express PSMA, which can be another limitation.

Even with a negative scan, patients should still receive treatment if intended for cure, as microscopic disease may be present that's too small to detect.

Dr. Calais reported that as of the previous Friday (March 28, 2025), the FDA approved Lutetium-PSMA therapy for metastatic castration-resistant prostate cancer patients pre-chemotherapy, meaning chemotherapy is no longer a requirement before receiving this treatment.

Clinical trials are now exploring using PSMA therapy even earlier in disease progression, including in hormone-sensitive patients.

Actinium is described as "the next big thing after Lutetium" - it's an alpha emitter that delivers much more energy in its radiation and may have more potent effects. Multiple trials are underway.

Dr. Calais highlighted that combining PSMA therapy with AR (androgen receptor) directed therapy may be impactful, with promising data emerging.

Regarding side effects, Dr. Calais confirmed the treatment is relatively side-effect free compared to chemotherapy, though it can cause fatigue and dry mouth in some patients.

Salivary gland damage remains a side effect with no significant progress in prevention, and the damage is irreversible. However, with Previcto (Lutetium-PSMA), the effect is generally mild and rare.

## Additional Information:

Dr. Calais mentioned that UCLA recently hosted a large PSMA conference with 300 attendees in person and 300 virtual participants, which included a patient sharing their experience with Lutetium-PSMA therapy.

UCLA offers second opinions on PSMA scans and MRIs, with contact information provided during the meeting.

When asked about PSA levels for PSMA scans, Dr. Calais explained that 0.2 is a reasonable threshold after surgery, but expectations should be adjusted based on PSA levels - at very low levels (0.1), one should expect potentially not seeing anything, while at higher levels (1.5), detection is more likely.

Dr. Calais clarified that theranostics (therapeutic diagnostics) is used for other cancers beyond prostate cancer, but with different targeting agents specific to those cancers.

Links referenced in the Presentation: 

• Radiology Connections at UCLA: https://www.uclahealth.org/medical-services/radiology/patient-resources/send-us-your-images-ucla-radiology-connections  

• Theranostics Trials:  https://www.theranostictrials.org/   

• Radiotheranostics:  https://www.oncidiumfoundation.org/  Phase 3 trial using the copper based: https://clinicaltrials.gov/study/NCT06056830  

• https://www.urotoday.com/urinary-catheters-home/indwelling-catheters/complications/1134-urotoday/prostate-cancer/157739-clarity-receives-u-s-fda-fast-track-designation-for-cu-64-sar-bispsma-in-biochemical-recurrence-of-prostate-cancer.html  

• https://www.claritypharmaceuticals.com/news/fda_amplify/