Getting Specific
By Keith Loria
Radiology Today
Vol. 25 No. 6 P. 22
Noteworthy Developments in Prostate Cancer Detection and Treatment
Modern imaging significantly improves the entire care pathway for patients with suspected and diagnosed prostate cancer. For example, MR facilitates earlier detection, more accurate diagnosis, personalized treatment plans, convenient followups, and tailored management of advanced disease.
Troy Havens, senior product manager for MR at Siemens Healthineers, says one of the most important new developments in the MR space when it comes to prostate cancer detection is imaging acceleration, which is driven by AI support. Siemens Healthineers has developed an AI-based reconstruction solution, Deep Resolve, which can reduce the typical prostate exam scan time by over 40%.
Another key driver Siemens Healthineers MRI has improved over the last three to four years is its imaging coil technology and the MR prostate exam. The ACR no longer recommends older, rectal-based MRI coils, so Siemens Healthineers now offers three different flexible types of lightweight and adaptable coils that contour to the patient’s body for improved patient comfort and imaging signal.
A third evolution in the industry comes in the form of overall MR planning and AI-based workflow optimization. Siemens Healthineers has developed a portfolio of MRI workflow assistance tools, packaged as myExam Assist, across 90% of all MR examinations. For MR prostate exams, myExam Prostate Assist aims to standardize multiparametric MRI of the prostate, assist less-experienced users in performing the scans, improve access for a larger opportunity of prostate imaging, and drive consistency and reproducibility in serial follow-up prostate exams, Havens says.
“The prostate exam is probably one of the more difficult exams for the MR technologist to plan and acquire,” he says. “myExam Prostate Assist guides the operator through one comprehensive workflow with decision points to adapt the strategy to individual patient conditions while artificial intelligence aids in planning and performing the procedure steps.” Looking ahead, Havens expects to see further development within the MR imaging reconstruction world but also sees a rise in using MR-only radiation simulation to do even more to support prostate cancer planning and therapy in the future.
177Lu-rhPSMA-10.1
Blue Earth Therapeutics has seen some promising early clinical data with 177Lu-rhPSMA (prostate-specific membrane antigen)-10.1, an investigational radiohybrid PSMA-targeted radiopharmaceutical for the treatment of prostate cancer, from the University Hospital Augsburg in Germany. David Gauden, CEO of Blue Earth Therapeutics, says the team at Augsburg has published the results from their early, investigator-led clinical experience with 177Lu-rhPSMA-10.1 in multiple settings.
For comparative dosimetry vs 177Lu-PSMA I&T, the results from this experience in four patients show that 177Lu-rhPSMA-10.1 had substantially higher absolute tumor-absorbed radiation dose and tumor:kidney ratio (therapeutic index) vs 177Lu-PSMA I&T. “In this report, three of four patients had PSA [prostate- specific antigen] reductions of >80%,” Gauden says. “Additionally, progression-free survival for individual patients at the time of data publication was 12 months, 15 months, 18 months (not reached), and 24 months (not reached). No serious safety findings were observed.”
In addition, 10 other patients have been treated with 177Lu-rhPSMA-10.1 as “rescue” therapy after experiencing progression while receiving cycles of 177Lu-PSMA I&T treatment, suggesting primary or acquired resistance to the radiation. This data was presented at the 2024 SNMMI annual meeting and is expected to be published later this year.
While 14 is a small number, researchers are encouraged by the Augsburg results and look forward to the ongoing Phase 1/2 clinical trial in the United States that is evaluating the safety, tolerability, dosimetry, and antitumor activity of 177Lu-rhPSMA-10.1 in eligible men with metastatic castrate-resistant prostate cancer.
Blue Earth Therapeutics’ aim was to design a molecule that remains in circulation long enough to achieve optimal uptake but not so long that normal organs receive intolerably high radiation doses. “We have designed the radiohybrid structure to allow ‘tunable’ pharmacokinetics and create the ideal properties,” Gauden says. “We know from our Phase 1 trial that the molecule has a long biological half-life in tumor deposits, and we pair this with a long-lived therapeutic radioisotope to maximize the dose to the tumor. Plasma and kidneys clear much more quickly, allowing the radioactivity to be excreted within the first day or so.”
Furthermore, more radiation to tumors leads to better clinical outcomes, and while it is possible to increase tumorabsorbed radiation doses by injecting higher doses of radioactivity, the upper limits are defined by normal organ dose limits. “Therefore, more efficient delivery of radiation in terms of tumor vs normal tissue (therapeutic index) is critical,” Gauden says. “This is where we believe the 177Lu-rhPSMA-10.1 advantage exists.”
As of summer 2024, the Phase 1 component of the trial is coming to an end. Predominantly, it is designed to characterize safety and radiation dosimetry in detail. The modeling from this dataset is informing the dosing regimens in Phase 2, which will commence later this year. “Blue Earth Therapeutics has several ongoing activities underway, including our Phase 1/2 trial, two investigator-initiated trials exploring the use of 177Lu-rhPSMA-10.1 in earlier clinical settings, and an additional study, which we will announce in due course,” Gauden says. “Regarding large-scale studies, we have a plan for pivotal registrational studies, which will be actioned based on the findings from our ongoing studies.”
This line of research is promising, and Gauden is excited that the first PSMAtargeted radioligand therapy (Pluvicto) has been shown to extend survival in men with post-taxane metastatic castrateresistant prostate cancer. “However, the survival benefit was modest vs a control arm that did not permit additional chemotherapy,” he says. “Blue Earth Therapeutics believes there is room for improvement by increasing the tumor-absorbed radiation dose while not increasing the dose to healthy organs. There are proven links between more radiation dose to tumors and survival outcomes.”
The company sees potential scope for use in a range of clinical settings for prostate cancer treatment, especially earlier in the disease continuum, if the long-term benefit:risk profile supports it. “The complementary mechanism of action of radiation with other therapies also opens up a number of intriguing trial designs which might even focus on turning some men from incurable to curable disease,” Gauden says.
Rise of Theranostics
In today’s prostate cancer care landscape, theranostics utilizes radiopharmaceutical PSMA agents for both imaging and treatment, allowing for a highly targeted and individualized treatment plan. PSMA is a biomarker that sits on the outside of prostate cancer cells and is detected by PET/ CT or SPECT/CT scans.
Lady Sawoszczyk, who leads the theranostics and collaboration team of the molecular imaging business at Siemens Healthineers, says the use of theranostics to treat prostate cancer has increased significantly in the past two years due to recent FDA approvals of PSMA therapeutic agents. “The use of PSMA PET/CT helps the physician select the right patient for the right treatment, as not every prostate cancer patient is a candidate for the theranostics approach,” she says. “PSMA is changing how we treat prostate cancer patients. You can have low PSA levels, and through PSMA PET/CT, you can image small lesions that are sometimes missed with CT and MRI.”
Once a prostate cancer patient is selected for theranostics treatment, that patient will undergo the infusion of the therapeutic agent. Prostate cancer patients who qualify for theranostics are receiving this treatment because they meet several criteria: they have not responded well to chemotherapy and hormone therapy, they have a history of mCRCP, and they have undergone a positive PSMA PET/CT scan.
“You can change these patients’ lives by extending those lives and improving their quality of life,” Sawoszczyk says, noting that theranostics is not a cure. “In the future, theranostics will be introduced earlier into the treatment regimen, as many clinical trials are being conducted.”
New Imaging Agent
Mary Jessel, Telix Pharmaceuticals Limited’s senior vice president for global medical affairs, has seen continuing advancements in the performance of scanner technology, resulting in a tremendous increase in prostate cancer detection sensitivity and patient workflow. “These advancements include longer axial field of view, increased time of flight, and improved detectors, resulting in faster acquisition times, higher resolution images, and greater sensitivity for lesion detection,” she says. “These technologies include United Imaging uExplorer, Siemens Vision Quadra, and GE Omni Legend, to name a few.”
As an example of how these advancements can improve prostate cancer detection and patient throughput, Telix, in collaboration with BAMF, provided the first-in-human application of a PSMA scan with Illuccix, Telix’s molecular imaging agent to detect prostate cancer, on the uExplorer. “Micrometastic lesions were identified in a total body scan in several minutes,” Jessel says. “The uExplorer has >500,000 detectors, allowing greater sensitivity gain, detecting 40x more signal for the same radiation dose. The same injected dose can improve the signalto- noise ratio by more than six times, thereby allowing a less effective radiation dose. These advanced imaging scanners increase the dynamic range of the radiotracer, while current scanners collect <1% of the available signal.” Additionally, advanced scanners are coupled with the growing field of AI, which can enable faster and more accurate identification of complex patterns, as well as quantify and evaluate radiographic traits.
Jessel says another example of molecular imaging advancing the standard of care is in PSMA-PET for the detection of prostate cancer. “The approval and access to PSMA-PET, compared to conventional imaging, has redefined how clinicians manage this disease,” she says. “PSMA is highly expressed 100- to 1,000-fold in prostate adenocarcinoma, which makes it a great molecular biomarker to detect prostate cancer, including where it has spread.”
Several examples include the following:
• A PSMA signal can be detected in small lymph nodes that show high avidity. This signal would potentially be missed on CT with a contrast study alone, as defined by lymph node dimensional size criteria.
• PSMA-PET’s ability to detect micrometastatic disease in patients with PSA levels as low as 0.2 ng/mL will change how we redefine biochemical recurrence.
• PET/MR PSMA whole-body imaging allows for excellent PET resolution and MR soft-tissue anatomic correlation for whole-body systemic metastatic assessment.
• Regional pelvic PET/MR imaging with smaller mpMRI fields of view for characterizing the prostate gland and locoregional lymph nodes can provide greater confidence for radiologists and urologists in interpreting images in the pelvis.
Telix recently submitted a New Drug Application to the FDA for TLX007-CDx, a proprietary cold kit for the preparation of PSMA-PET imaging for prostate cancer. Once approved, the cold kit will allow the use of a PSMA imaging product with a significantly extended distribution profile when compared with currently approved gallium-68 PSMA-PET imaging agents. This investigational prostate cancer imaging product is designed to address the unmet needs of patients, referrers, and health care professionals and expand patient reach using Telix’s established nuclear pharmacy distribution partnerships.
Lead-212
A novel SPECT/CT acquisition method— known as lead-212 (212Pb)—can accurately detect radiopharmaceutical biodistribution in a convenient manner for prostate cancer patients. Due to a shortage of the isotope actinium, there’s not enough to support clinical trials or patients, so there is a clinical need for radionuclides such as 212-Pb, which is made in a generator and more widely available.
Tom Hope, MD, a nuclear medicine physician at the University of California, San Francisco, says 212-Pb allows imaging of an alpha-emitter with a standard SPECT camera and standard collimator, which could lead to better precision in treating patients with prostate cancer. He adds that the clinical impact of 212Pb-PSMA-based targeted alpha therapy on patients with mCRCP is more effective than imaging with actinium-225.
“Lead is better than actinium for imaging on SPECT because it has more gamma emissions, so you can image lead- 212 better than you can actinium-225,” Hope says. “This is the beginnings of a new radionuclide, enabling better alpha label therapies.”
— Keith Loria is a freelance writer based in Oakton, Virginia. He is a frequent contributor to Radiology Today.
