Multi-Tracer PET Approach Offers Personalized Management of Advanced Prostate Cancer

Reston, VA (November 14, 2024)—A new whole-body multi-tracer PET imaging approach can accurately identify evolving subtypes of cancer cells within distinct metastases in the same prostate cancer patient, according to new research published in The Journal of Nuclear Medicine. These changing cancer cells, found in different metastases from the same patient—known as intrapatient intermetastatic heterogeneity (IIH)—were found in 83 percent of metastatic castration-resistant prostate cancer (mCRPC) patients. Understanding their characteristics can provide physicians with valuable insights for developing personalized treatment plans.

Advances in medicine now allow mCRPC patients to undergo several types of treatment targeting different cancer pathways. Multiple treatments, however, cause cancer cells to change, resulting in IIH. These changes to challenges in monitoring cancer treatment resistance, defining progression, and making therapeutic decisions.

“Prior to this study, evidence of IIH in prostate cancer was determined by biopsy from only a few metastatic sites, either late in the disease course or after rapid autopsy,” said Frédéric Pouliot, MD, PhD, FRCSC, clinician-scientist and associate professor in the department of surgery, urology division, at CHU de Québec–Université Laval Research Center in Quebec City, Quebec, Canada. “By using whole-body PET/CT to scan for IIH earlier, clinicians can integrate IIH knowledge in their treatment decisions, including radiopharmaceutical therapy.”

In the study, authors assessed the prevalence of IIH in mCRPC and its associated impact on overall survival. Whole-body PET imaging was conducted with three distinct PET tracers (¹⁸F-FDG, ⁶⁸Ga-PSMA-617, and ⁶⁸Ga-DOTATATE). Ninety-eight patients were included in the primary analysis, which included ¹⁸F-FDG and ⁶⁸Ga-PSMA-617 PET/CT scans. Thirty-seven patients who were found to have at least one ¹⁸F-FDG-positive/⁶⁸Ga-PSMA-617-negative lesion received an additional ⁶⁸Ga-DOTATATE PET/CT scan.

IIH prevalence in the 98 patients receiving ¹⁸F-FDG and ⁶⁸Ga-PSMA-617 PET/CT scans was 82.7 percent. In the patients who underwent ⁶⁸Ga-DOTATATE PET/CT, the prevalence of IIH was 83.8 percent, and 16.2 percent had positive lesions. Based on the individual metastasis uptakes of the three tracers in each patient, at least 12 different mCRPC IIH combinations were found.

The overall survival of all enrolled patients was 10.2 months. Patients with IIH had a median overall survival of only 9.5 months and a 2.7-fold higher probability of dying of prostate cancer during the study follow-up than those without IIH. Those with at least one ¹⁸F-FDG-positive/⁶⁸Ga-PSMA-617-negative lesion had a median overall survival of only 5.6 months and a 2.8-fold higher probability of dying of prostate cancer during the study follow-up than those with only ⁶⁸Ga-PSMA-617-positive lesions. Finally, patients who had at least one ⁶⁸Ga-DOTATATE-postive lesion had a poor median overall survival of 3.0 months and a 5.0-fold higher probability of dying of prostate cancer during the study follow-up than those without.

“These findings show an unexpected high prevalence of IIH in mCRPC patients and demonstrate that IIH and some patterns of tracer positivity are associated with decreased survival,” noted Pouliot. “In the future, molecular imaging with multiple tracers may have a novel and important role for precision medicine in mCRPC and other cancers.”

Figure 3. Patient with five different lesion phenotypes seen on triple-tracer PET/CT imaging. (A) Coregistered transaxial slices of whole-body maximum-intensity projection PET/CT showing multiple metastases with three different radiopharmaceuticals. (B) Discordant expression of five representative lesions: bone lesions of seventh left rib (first row) and left scapula (second row), lesions in left iliac (third row) and left supraclavicular (fourth row) lymph nodes, and lesion in right liver lobe (fifth row).

The authors of “Intrapatient Intermetastatic Heterogeneity Determined by Triple-Tracer PET Imaging in mCRPC Patients and Correlation to Survival: The 3TMPO Cohort Study” include Frédéric Pouliot, Oncology Axis, CHU de Québec–Université Laval Research Center, Quebec City, Quebec, Canada, and Division of Urology, Department of Surgery, Université Laval, Quebec City, Quebec, Canada; Fred Saad and Jean-Baptiste Lattouf, Division of Urology, Department of Surgery, Centre Hospitalier de l’Université de Montréal, Université de Montréal, Montréal, Quebec, Canada; Etienne Rousseau and Brigette Guérin, Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, Sherbrooke, Quebec, Canada, and Sherbrooke Molecular Imaging Centre, Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada; Patrick O. Richard, Division of Urology, Department of Surgery, Centre Hospitalier Universitaire de Sherbrooke and Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada; Atefeh Zamanian, Oncology Axis, CHU de Québec–Université Laval Research Center, Quebec City, Quebec, Canada, and Department of Radiology and Nuclear Medicine, and Cancer Research Centre, Université Laval, Quebec City, Quebec, Canada; Stephan Probst, Division of Nuclear Medicine, Faculty of Medicine, Sir Mortimer B. Davis–Jewish General Hospital, McGill University, Montréal, Quebec, Canada; Éric Lévesque, Vincent Castonguay, and Micolas Marcoux, Division of Hemato-Oncology, Department of Medicine, CHU de Québec–Université Laval, Quebec City, Quebec, Canada; Michele Lodde, Surgery Urology Department, CHU de Québec–Université Laval, Quebec City, Quebec, Canada; Daniel Juneau, Nuclear Medicine, Centre Hospitalier de l’Université de Montréal, Montreal, Quebec, Canada; Zinb Hamilou, Hemato-Oncology, Centre Hospitalier de l’Université de Montréal, Montreal, Quebec, Canada; François-Alexandre Buteau, Department of Radiology and Nuclear Medicine, and Cancer Research Centre, Université Laval, Quebec City, Quebec, Canada, and Division of Nuclear Medicine, Department of Medical Imaging, CHU de Québec–Université Laval, Quebec City, Quebec, Canada; Michel Pavic and Jean- François Castilloux, Medical Oncology, Centre Intégré Universitaire de Santé et Services Sociaux de l’Estrie–Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada; Bertrand Neveu and Guillaume F. Bouvet, Oncology Axis, CHU de Québec–Université Laval Research Center, Quebec City, Quebec, Canada; Catherine Allard and Amélie Tétu, Unité de Recherche Clinique et Épidémiologique, Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada; and Jean-Mathieu Beauregard, Oncology Axis, CHU de Québec–Université Laval Research Center, Quebec City, Quebec, Canada, Department of Radiology and Nuclear Medicine, and Cancer Research Centre, Université Laval, Quebec City, Quebec, Canada, and Division of Nuclear Medicine, Department of Medical Imaging, CHU de Québec–Université Laval, Quebec City, Quebec, Canada.

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