PSMA-PET Reduces Prostate Deaths

Using PSMA-PET instead of conventional imaging to stage patients with recurrent prostate cancer could reduce deaths by 13% and lead to improved quality of life. The new paper in JAMA Network Open confirms the value of PSMA imaging compared to traditional imaging approaches. 

Recurrent prostate cancer is one of the trickiest cancers to manage, especially as biochemical recurrence can occur in up to half of patients getting local treatment. 

  • PSA tests work well for detecting rising prostate antigen levels that could signify recurrence, but it can be difficult to locate recurrent cancer with existing imaging tools like CT and bone scans.

PET using a new generation of PSMA tracers offers a better solution thanks to tracers that target the PSMA protein that builds up on the surface of prostate cancer cells.

  • Previous studies have shown that PSMA-PET is more sensitive and specific for detecting recurrent prostate cancer, especially at lower PSA levels – but the modality’s long-term effects haven’t been explored. 

In the new study, researchers wanted to investigate the impact of switching to PSMA-PET on mortality and quality of life using statistical modeling to predict outcomes from three imaging approaches …

  • Conventional imaging with CT and bone scan.
  • CT and bone scan followed by PSMA-PET for negative or equivocal cases.
  • PSMA-PET alone.

They then projected outcomes for a hypothetical population of 1k patients with biochemically recurrent prostate cancer, defined as a persistent or rising PSA of 0.20 ng/mL after prostatectomy or PSA 2.0 ng/mL or higher following radiation therapy. They found …

  • PSMA-PET had the lowest number of prostate cancer deaths at 512, compared to conventional imaging plus PSMA-PET (520) or just conventional imaging (587).
  • PSMA-PET diagnosed 611 patients with metastasis compared to 630 with conventional imaging plus PSMA-PET and 297 with only conventional imaging.
  • PSMA-PET yielded 824 more quality-adjusted life years per 1k patients than conventional imaging.

The Takeaway

The findings are not only good news for patients with recurrent prostate cancer, they are also a boon for developers of commercially available PSMA-PET radiotracers like Lantheus Medical Imaging’s Pylarify (approved in 2021), Telix Pharmaceuticals’ Illuccix (approved in 2021), and Blue Earth Diagnostics’ Posluma (approved in 2023). 

Next-Generation Brain PET

A new paper in JNM includes the first human images acquired with a next-generation dedicated brain PET/CT scanner that could create a new standard for neurological research. United Imaging’s NeuroEXPLORER scanner has sensitivity and spatial resolution “an order of magnitude” better than existing technology. 

In addition to its value as a clinical tool, PET has carved out a research role for investigating some of the most fundamental questions about brain function and pathology. 

  • Commercial whole-body scanners can be used for research, but dedicated brain systems like the High Resolution Research Tomograph (HRRT) offer even higher resolution for imaging tiny structures in the brain. 

NeuroEXPLORER was developed by a consortium that includes United Imaging, UC Davis, and Yale University to adapt for dedicated brain imaging the long-axis PET technology found in United’s uEXPLORER total-body PET/CT system. 

  • NeuroEXPLORER was a highlight at the recent SNMMI 2024 conference, and images acquired with the system won the show’s coveted Image of the Year honors.

In the new study, researchers go into more detail about NeuroEXPLORER’s specifications, which include … 

  • An extended axial field of view (FOV) of 49.5cm for higher sensitivity
  • Transverse spatial resolution ranging from 1.64-2.51mm at full-width half-maximum
  • Average time-of-flight resolution of 236 picoseconds
  • NEMA sensitivities of 46.0 and 47.6 kcps/MBq at center and 10cm offset, and absolute sensitivity of 11.8% at the center of the FOV

Such high sensitivity and spatial resolution enables tasks “previously considered difficult or impossible,” like imaging focal tracer uptake of small subcortical regions or low-density binding sites like cortical dopamine receptors. 

  • What’s more, NeuroEXPLORER’s long axial length enables high-quality imaging of the spinal cord and carotid arteries.

Now for the disclaimer: United Imaging notes that NeuroEXPLORER has not been submitted to the FDA for clearance and at present is only for research use; the company’s uEXPLORER scanner does have clearance and is in operation at several commercial sites. 

The Takeaway

Publication in a journal of the first human images from NeuroEXPLORER are an exciting development and underscore the potential of dedicated brain PET to advance research into neurological function and pathology. Whether the scanner develops into a clinical tool remains to be seen.

Headlines from SNMMI 2024

SNMMI 2024 wrapped up this week in Toronto, Canada, with the conference once again demonstrating the utility of nuclear medicine and molecular imaging for applications ranging from neurology to oncology to therapeutics. 

An annual SNMMI highlight is always the Image of the Year designation, and this year’s meeting didn’t disappoint. 

  • The honor went to a set of ultra-high-resolution brain PET images acquired with United Imaging’s NeuroEXPLORER (NX) scanner, a PET/CT system that the company developed with Yale and UC Davis and introduced last year for research use (although a clinical introduction could be forthcoming). 

The NX system sports a cylindrical design with a 52.4cm diameter and long axial field-of-view of 49.5cm; in the talk presented at SNMMI, researchers compared it to high-resolution research tomograph images with tracers targeting different dopamine receptors and transporters.

  • Researchers said the NX system had “exceptional” resolution in cortex and subcortical structures, with “low noise and exquisite resolution,” and predicted NX would “dramatically expand the scope of brain PET studies.”

Other important presentations at SNMMI included papers finding … 

  • An AI algorithm developed at Johns Hopkins detected six different types of cancer and automatically quantified tumor burden on whole-body PET/CT scans
  • In a study of 10.5k patients, AI that analyzed SPECT/CT images was able to predict all-cause mortality with an AUC of 0.77 by using CT attenuation correction scans to calculate risk factors like coronary artery calcium
  • Cognitive training is less effective in older adults who have beta-amyloid deposits in the brain on PET scans
  • An ultra-low-dose PET protocol presented by researchers from Bern University Hospital in Switzerland and Siemens Healthineers used deep learning reconstruction for a 50X reduction in PET radiation dose, to 0.15 mSv
  • A gallium-68 FAPI-based PET radiotracer was more accurate than fluorine-18 FDG for systemic staging of newly diagnosed breast cancer
  • A new chelating agent that binds radiometals to the parts of molecules that target cancer reduced off-target toxicity in PSMA radiopharmaceutical therapy
  • A combination of alpha- and beta-radionuclide therapy that combined actinium-225 with lutetium-177 worked well for colorectal cancer in a preclinical study
  • Research sponsored by Novartis on radioligand therapy for prostate cancer with lutetium-177 PSMA-617 (Pluvicto) was chosen as Abstract of the Year

The Takeaway

This year’s SNMMI presentations highlight the exciting advances taking place in nuclear medicine and molecular imaging, with the rise of theranostics giving the field an entirely new wrinkle that places it even closer to the center of precision medicine. Perhaps a new letter – T – will need to be added to the conference before too long.

Nuclear Medicine’s AI Uptake

Nuclear medicine is one of the more venerable medical imaging technologies. Artificial intelligence is one of the newest. How are the two getting on? That question is explored in new point-counterpoint articles in AJR

Nuclear medicine was an early adopter of computerized image processing, for tasks like image analysis, quantification, and segmentation, giving rise to a cottage industry of niche software developers.

  • But this early momentum hasn’t carried over into the AI age: on the FDA’s list of 694 cleared AI medical applications through July 2023, 76% of the listed devices are classified as radiology, while just four address nuclear medicine and PET.

In the AJR articles, the position that AI in nuclear medicine is more hype than reality is taken by Eliot Siegel, MD, and Michael Morris, MD, who note that software has already been developed for most of the image analysis tasks that nuclear medicine physicians need. 

  • At the same time, Siegel and Morris say the development of AI-type algorithms like convolutional neural networks and transformers has been “relatively slow” in nuclear medicine. 

Why the slow uptake? One big reason is the lack of publicly available nuclear medicine databases for algorithm training. 

  • Also, nuclear medicine’s emphasis on function rather than anatomical changes means fewer tasks requiring detection of subtle changes.

On the other side of the coin, Babak Saboury, MD, and Munir Ghesani, MD, take a more optimistic view of AI in nuclear medicine, particularly thanks to the booming growth in theranostics. 

  • New commercial AI applications to guide the therapeutic use of radiopharmaceuticals are being developed, and some have received FDA clearance. 

As for the data shortage, groups like SNMMI are collaborating with agencies and institutions to create registries – such as for theranostics – to help train algorithms. 

  • They note that advances are already underway for AI-enhanced applications such as improving image quality, decreasing radiation dose, reducing imaging time, quantifying disease, and aiding radiation therapy planning. 

The Takeaway
The AJR articles offer a fascinating perspective on an area of medical imaging that’s often overlooked. While nuclear medicine may never have the broad impact of anatomical-based modalities like MRI and CT, growth in exciting areas like theranostics suggest that it will attract AI developers to create solutions for delivering better patient care.

Theranostics Grabs SNMMI Spotlight

The emerging field of theranostics – in which two radiopharmaceuticals work in tandem for diagnostic and therapeutic purposes – is one of the most exciting new areas of medicine. Nowhere is this more evident than at this week’s SNMMI 2023 meeting in Chicago

Theranostics involves the use first of a highly targeted diagnostic radiotracer to detect pathology with a technology like PET, then sending in another tracer to deliver a stronger radioactive payload to the site of disease – almost the definition of precision medicine. Some estimates are that theranostics could soon develop into a market worth $30B.

In addition to talks on theranostics, SNMMI 2023 highlights so far have included presentations covering the following:

  • An ultra-high-resolution brain PET scanner that can visualize and quantify nuclei in the brainstem for the first time, opening up new inquiries into neurological disorders like Alzheimer’s disease
  • The discovery of the optimal tracer kinetic model for quantifying myocardial uptake of 18F-flutemetamol in patients with transthyretin (ATTR) cardiac amyloidosis, a buildup of amyloid plaque in the heart
  • A technique called augmented whole-body scanning via magnifying PET (AWSM-PET) that uses two high-resolution add-on detectors as an “outsert” to improve image resolution and reduce noise
  • Imaging of rheumatoid arthritis with 68Ga-FAPI PET/CT, which showed a greater number and degree of affected joints than FDG-PET/CT
  • A PET radiotracer called 18F-Cholestify has the potential to improve neuroimaging by visualizing metabolic cholesterol degradation in the brain.

The commercial side of SNMMI 2023 is active as well. Siemens Healthineers, GE HealthCare, and United Imaging Healthcare are launching new hybrid scanners, and other vendor news includes the following: 

  • Blue Earth Diagnostics is touting its recent shipments of Posluma, a PET radiotracer targeting PSMA in prostate cancer patients
  • GE HealthCare is migrating AIR technologies found on its MRI scanners to its new Signa PET/MRI AIR system (see below) 
  • Isotopia is discussing its plans for a US radioisotope manufacturing facility
  • Lantheus researchers are presenting talks on AI-enabled PSMA-PET reporting using its Pylarify AI software
  • Mediso received FDA clearance for its InterView Fusion and InterView XP multimodality image processing and reporting software
  • Siemens Healthineers has launched a new PET/CT scanner, Biograph Vision.X, sporting a 20% improvement in time of flight (see below)
  • Subtle Medical is demonstrating its SubtlePET solution, which uses AI to remove noise for low-count PET images, enabling up to 75% faster PET scans
  • Telix Pharmaceuticals is highlighting clinical results of several agents: the Illuccix gallium-based prostate cancer imaging agent; ProstACT lutetium-based antibody-directed prostate cancer therapy; and TLX250-CDx, a zircon-89-based tracer for diagnosing clear cell renal cell carcinoma.
  • United Imaging Healthcare is launching uMI Panorama, a new wide-bore PET/CT scanner (see below).  

The Takeaway

This week’s proceedings in Chicago illustrate the new energy that theranostics is bringing to nuclear medicine and molecular imaging, one of radiology’s most venerable modalities. Stay tuned for the announcement of SNMMI’s Henry N. Wagner, Jr. Image of the Year award, always a conference highlight.  

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