Borderline Molecular Targeted Imaging Results: Case Studies

How to cite: Helfand BT. Borderline Molecular Targeted Imaging Results: Case Studies. Grand Rounds in Urology. February 2026. Accessed Apr 2026. https://grandroundsinurology.com/borderline-molecular-targeted-imaging-results-case-studies/

Summary

Brian T. Helfand, MD, PhD, is Chief Emeritus of the Division of Urology and an Associate Chief Scientific Officer at Endeavor Health, Evanston, Illinois, presents real-world case studies highlighting diagnostic uncertainty in molecular targeted imaging, emphasizing biologic variability, technical limitations, and interpretation challenges that influence management decisions.

Molecular targeted imaging, particularly prostate-specific membrane antigen positron emission tomography (PSMA PET), has rapidly become integrated into prostate cancer staging and biochemical recurrence assessment. Despite improved detection compared with conventional imaging, important limitations remain.

PSMA is not entirely prostate-specific. Physiologic uptake in salivary glands, peripheral nerves, ganglia, and urinary structures can create false positives. Resolution limits remain approximately 4 millimeters, restricting detection of microscopic disease. Tumor heterogeneity further complicates interpretation, including variable expression across lesions, neuroendocrine differentiation, and potential genomic influences such as BRCA2 mutation status.

Reader variability also contributes to diagnostic discordance. Many trials rely on expert readers and adjudication systems that may not reflect routine practice.

Case 1 involves a patient with slowly rising prostate-specific antigen after prostatectomy and multiple previously negative scans who develops faintly avid pulmonary micronodules. Low standardized uptake values and the absence of prior abnormalities create uncertainty about whether findings are metastatic or benign. Observation with serial imaging is favored.

Case 2 demonstrates uptake near the celiac region with a low standardized uptake value, interpreted as ganglion rather than lymph node metastasis. Salvage pelvic radiation with androgen deprivation therapy is pursued despite negative pelvic imaging, underscoring the importance of clinical context.

Case 3 presents a BRCA2-positive patient with high-risk localized disease and a solitary rib lesion with low avidity and negative magnetic resonance imaging. Sequential local therapy is chosen with surveillance of the equivocal lesion.

Case 4 highlights incidental thyroid uptake with moderate avidity, raising questions regarding incidentalomas unrelated to prostate cancer.

Dr. Helfand emphasizes cautious interpretation, multidisciplinary review, and an understanding of biological and technical limitations before altering management based solely on imaging findings.

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