Healthcare Is Personal: Precision Health & Theranostics for Personalized Prostate Cancer Care

With the development of next-generation alpha- and beta-labeled radiotherapeutics and the use of the most recent diagnostic PET radiopharmaceuticals, nuclear medicine is entering a new era of precision theranostics.

Theranostics integrates diagnosis and treatment in one application, offering a more targeted and individualized therapy than ever before, in contrast to most medical therapies that are created with the "average" patient in mind.

Prostate cancer, which claims more than 1.4 million lives each year but is highly treatable when detected early on, is one ailment that theranostics is particularly effective in treating, according to doctors and patients [1].

During the COVID-19 pandemic, clinical adoption of theranostics slowed due to a delay in elective procedures and the increased risk posed to its often-immunocompromised patients.

However, a rise in demand for theranostics infrastructure [2] is now anticipated in light of the FDA's recent approval of a number of new medications and treatments. This comprises the crucial theranostic tools for the treatment of prostate cancer, lutetium-177 PSMA-617 and the diagnostic tracer gallium-68 PSMA-11.

Theranostics has the potential to transform care from a look at the ‘average’ patient to a precise look at ‘each’ individual.

By assisting with the identification of the disease, the precise assessment of its course, and the delivery of targeted, individualized therapy - all in the same session - it is already giving hope to late-stage prostate cancer patients.

And soon, we hope to see it adopted earlier in the disease care pathway and across oncology to benefit more patients around the world.

The Society of Nuclear Medicine and Molecular Imaging (SNMMI) and allied international molecular imaging associations recently released a new roadmap for healthcare systems worldwide [2] to help them become ready for the opening of dedicated theranostics facilities.

The guide presents a framework that highlights best practices that may be applied across care areas, with a focus on safety protocols and operational procedures.

The future is here with the FDA's clearance of a new PSMA-agent for the treatment of prostate cancer. The demand for theranostics from patients, their families, and referring doctors is unparalleled, driving up the need for ever-higher doses of radioactive elements. Commercial solid-target products fit for normal usage are the sole method to provide the world's need for PET radionuclides like gallium-68 and copper-64.

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Discovery with the Molecule Journey: Enabling Precision Health

The production of radioisotopes for use in diagnostic tracers, such as Gallium-68 PSMA-11, which is administered to the patient, attaches to specific cancer cells, and emits radioactive emissions to provide comprehensive molecular information specific to each patient, is the first step in enabling theranostics in the treatment of prostate cancer.

However, shortages of the generators that produce Gallium-68 historically have created serious challenges for clinicians and limited patient access. In response, GE Healthcare is proud to introduce a new Solid Target Platform for its PETtrace cyclotron which – in combination with its FASTlab 2 New Edition platform – can produce 100x the amount of Gallium compared to a generator for increased theranostics capabilities and access in prostate cancer patient care [3].

Although solid targets have been around for a while, they have typically been considered research tools since they require a complex infrastructure and operators with advanced training. Now that GE Healthcare has introduced the new PETtrace Solid Target Platform and TRACER center Solutions, healthcare systems can more quickly gain access to the tools, tracers, and staff training required to provide a more customized, cost-effective solution.

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Diagnosis: Accurately Staging & Quantifying Disease

To read the emissions released by the Gallium-68 PSMA-11 tracer, the patient must be imaged using a highly sensitive PET/CT scanner. This technology provides the clinician detailed information that is used to better understand the structure and function of each patient’s tissue and disease state to help form personalized therapy recommendations. The more sensitive the PET/CT, the more accurate the images and quantification.

GE Healthcare’s Discovery MI Gen 2 premium digital PET/CT systemoffers next-generation digital detection with an axial field of view (FOV) adjustable up to 30 centimeters to achieve a 125 percent increase in sensitivity [4]. The scan times or dose quantities can be improved by up to 33% as a result [5].

These capabilities are further supported by Q.Clear, which offers up to 2x improvement in both image quality (SNR) and quantitation accuracy (SUV [6]), and MotionFree for up to 67 percent improvement in lesion volume measurements, helping inform clinicians’ prostate cancer therapy recommendations [7].

Additionally, this scanner includes a CT that is designed to allow TrueFidelity deep-learning image reconstruction to enable image sharpness and improved noise texture [8]. Discovery MI Gen 2 proclaims up to a 41 percent increase in small lesion detectability [9].

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Treatment: Delivering & Monitoring Targeted Therapy

Regarding therapy, the FDA recently approved Lutetium-177 PSMA-617 – an exceptional therapy for advanced prostate cancer – in March 2022. It works by binding to and delivering a small amount of radiation to prostate cancer cells anywhere in the body to help patients with advanced prostate cancer live longer and maintain quality of life [10].

To help clinicians evaluate the success of these therapies, GE Healthcare developed its breakthrough StarGuide SPECT/CT system with 12 cutting-edge CZT detectors that not only scan patients in 3D to provide more information to clinicians but are also optimized for Theranostics procedures – including imaging this latest Lutetium-177-based prostate cancer therapy.

Compared to conventional technologies, StarGuide’s Digital Focus CZT detectors offer improved volume sensitivity and SPECT resolution [11], which is especially valuable for imaging both peaks of Lutetium-177 emissions, which in turn helps clinicians pinpoint the size, shape, and position of lesions with exceptional accuracy. Paired with GE Healthcare’s innovative Q.Clear solution for SPECT reconstruction, the resulting images provide outstanding quantification for the diagnosis and staging of disease and monitoring of treatment.

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Accuracy and Efficiency Improvements

In today's resource-constrained healthcare environment, artificial intelligence (AI) also presents new chances to optimize workflows, deliver reliable data, and speed up diagnosis across care domains.

That’s why GE Healthcare also offers the Xeleris V image processing solution with a collection of AI-enabled clinical applications to help simplify and enhance workflows. This includes Q.Thera AI [12], which is designed to leverage Q.Volumetrix MI to help clinicians automatically and accurately segment areas of interest – including AI-based kidney segmentation – for quantitation and dosimetry calculations, all with the goal to help reduce the time required for the user to process and calculate dose – enabling them to spend more time with patients.

The advancement of imaging technologies and continuous evolution and discovery of new tracers and targeted therapies is ushering in a new era in healthcare – one in which precision health and theranostics exist at its core. Prostate cancer is only the beginning, with many more applications under development for the future.

GE Healthcare is proud to offer clinicians unique opportunities to make personalized care decisions and treatment response assessments for the benefit of patients around the world.

GE Healthcare is uniquely positioned to advance these efforts as the only partner with solutions spanning from molecular imaging diagnostics, cyclotrons, chemistry synthesis, PET/CT, PET/MR, nuclear medicine, advanced digital solutions, and pharma partnerships to cover the breadth of steps from discovery to diagnosis to treatment.

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References

1)????“Cancer” World Health Organization. Feb 3, 2022. Accessed August 23, 2022.?https://www.who.int/news-room/fact-sheets/detail/cancer

2)?????“JNM Publishes Joint Guide for the Establishment of Theranostics Centers.” Society of Nuclear Medicine. Apr 29, 2022.?https://www.snmmi.org/NewsPublications/NewsDetail.aspx?ItemNumber=40416

3)?????Svedjehed et al. “Demystifying solid targets: Simple and rapid distribution-scale production of [68Ga]GaCl3 and [68Ga]Ga-PSMA-11.”?Nuclear Medicine and Biology. Volumes 104–105, January–February 2022, Pages 1-10.?https://doi.org/10.1016/j.nucmedbio.2021.10.002

4)?????Sensitivity (cps/kBq) as compared to Discovery MI 20 cm.

5)?????With Discovery MI Gen 2 30 cm configuration compared to 25 cm configuration. 33% reduction in scan time or injected dose, as shown in phantom testing.

6)?????SNR and SUV improvement as compared to OSEM.

7)?????Compared to non-processed (STATIC, no motion correction) data. As demonstrated in phantom testing using a typical and fast respiratory model, 18 mm Ge-68 spheres, and OSEM reconstruction.

8)?????As demonstrated in a clinical evaluation consisting of 60 cases and seven physicians, where each case was reconstructed with both DLIR and ASiR-V? and evaluated by three of the physicians. In 90 percent of the reads, DLIR’s noise texture was rated better than ASiR-V’s. In 99 percent of the reads, DLIR’s image sharpness was rated the same as or better than ASiR-V’s.

9)?????Discovery MI Gen 2 30 cm compared to Discovery MI 25 cm with matched scan time/injected dose. As demonstrated in phantom testing.

10) “Breaking News: First-in-Class Radioligand Therapy Approved for Advanced Prostate Cancer,” Prostate Cancer Foundation. March 23, 2022.?https://www.pcf.org/c/breaking-news-first-in-class-radioligand-therapy-approved-for-advanced-prostate-cancer/#:~:text=Lutetium%2DPSMA%2D617%20(Lu%2DPSMA)%20is%20now,and%20taxane%2Dbased%20chemotherapy

11) StarGuide SPECT reconstruction with scatter used the system’s factory NEMA NU 1-2018 resolution protocol which uses the same method (BSREM with Clarity 3D) as its clinical bone protocol. NM/CT 870 DR and NM/CT 870 CZT SPECT reconstruction used Evolution for Bone (OSEM). NM/CT 870 DR used LEHR/LEHRS collimators and NM/CT 870 CZT used the WEHR collimator.

12) CE marked. 510k pending with the FDA. Not available for sale in all regions.

Note: Radiopharmaceuticals may not be approved by ministers of health in all regions. Gallium-68 PSMA-11 and Lutetium-177 PSMA-617 are not approved in Canada.