Faculty Bibliography

BACKGROUND/UNASSIGNED:I-PU-H71 is an imaging biomarker of epichaperome formation. The tracer has been established to localize in tissues under chronic stress, specifically in cancer cells and neurodegenerative brain cells. A first-in-human imaging trial using positron emission tomography (PET) in cancer patients revealed unexpected tracer accumulation in the myocardium. PURPOSE/UNASSIGNED:I-PU-H71 myocardial biodistribution and pharmacokinetics in a series of cancer patients with no history of cardiovascular disease. METHODS/UNASSIGNED:I-PU-H71 while at rest, followed by dynamic and gated/non-gated PET image data acquisitions. Region-of-interest (ROI) analysis of left ventricular myocardium (LVmyo) and background left atrium quantified tracer concentrations as standardized uptake value (SUV) and uptake ratios. Kinetic rate constants were evaluated by a two-tissue compartment model. RESULTS/UNASSIGNED:(IQR, 0.0015-0.0057). Regional assessment demonstrated essentially uniform tracer uptake in LV and myocardial segments; with normal LVEF in all patients (mean 57.7 ± 3.5%); and no patients suffered cardiac events over subsequent 12-month period. CONCLUSION/UNASSIGNED:I-PU-H71 PET. Our data indicates PU-H71 PET merits further study as a myocardial epichaperome biomarker, with potential application in drug development, possibly as a biomarker in subclinical cardiac dysfunction.

Somatostatin receptor imaging using 68Ga-DOTATATE PET is widely popular for evaluation of neuroendocrine tumors. 68Ga-DOTATATE PET/CT shows highest physiologic uptake in spleen followed by other organs such as kidneys, adrenal glands, and liver. Hemangiomas, although rare, are the most common primary benign neoplasm of the spleen, composed of endothelial-lined vascular channels. We present a case of 77-year-old man who underwent 68Ga-DOTATATE PET/CT scan for evaluation of pancreatic neuroendocrine tumor and incidentally demonstrated intense radiotracer uptake in splenic hemangiomata.

To investigate diagnostic and prognostic value of ¹⁸F-FDG PET/CT for surveillance imaging in patients treated for Stage III Merkel cell carcinoma (MCC). Methods: This retrospective study included 61 consecutive stage III MCC patients, who were clinically asymptomatic and underwent surveillance FDG-PET/CT. Findings were correlated with either pathology and/or clinical/imaging follow-up. Median follow-up period was 4.8 years. Statistical analyses were performed. Results: FDG-PET/CT detected unsuspected recurrences in 33% patients (20/61) with lesion-based sensitivity, specificity, and accuracy of 92%, 93%, and 93%, respectively. Mean±SD SUV for malignant and benign lesions was 7.5±3.9 and 3.8±2.0, respectively. Unknown distant metastases, as first recurrence site, were noted in 12 of 61 patients. Those with positive disease on FDG-PET/CT within one year of definitive treatment had relatively worse overall survival (p<0.0001). After adjustment on stage, risk of death increased with higher SUV_max (HR for one unit=1.17;P = 0.006) and with a higher number of positive lesions on FDG-PET/CT (HR for one additional lesion = 1.60;p<0.001). Conclusion: Post-definitive treatment surveillance FDG-PET/CT scan detects unsuspected recurrences and has prognostic value. Inclusion of FDG-PET/CT within the first 6 months after definitive treatment would be appropriate for surveillance and early detection of recurrence. Our data merits further studies to evaluate the prognostic implications.

Prostate specific membrane antigen (PSMA) is a transmembrane protein that is highly expressed on prostate epithelial cells and is strongly upregulated in prostate cancer. Radioligand therapy using beta-emitting Lutetium-177 (¹⁷⁷Lu)-labeled-PSMA-617, a radiolabeled small molecule, has gained attention as a novel targeted therapy for metastatic prostate cancer, given its high affinity and long tumor retention, and rapid blood pool clearance. In March 2022, the United States Food and Drug administration has granted approval to the targeted ¹⁷⁷Lu-PSMA-617 therapy for treatment of patients with PSMA-positive metastatic castration resistant prostate cancer, who have been previously treated with an androgen-receptor pathway inhibitor and taxane-based chemotherapy. Studies have demonstrated the adverse effects of this treatment, mainly encountered due to radiation exposure to non-target tissues. Salivary glands show high PSMA-ligand uptake and receive increased radiation dose secondary to accumulation of ¹⁷⁷Lu-PSMA-617. This predisposes the glands to radiation-mediated toxicity. The exact mechanism, scope and severity of radiation-mediated salivary gland toxicity are not well understood, however, the strategies for its prevention and treatment are under evaluation. This review will focus on the current knowledge about salivary gland impairment post ¹⁷⁷Lu labeled PSMA-based radioligand therapies, diagnostic methodologies, and imaging with emphasis on salivary gland scintigraphy. The preventive strategies and known treatment options would also be briefly highlighted.

A 68-year-old man with a history of prostate cancer post-primary treatment presented with rising prostate-specific antigen levels and was referred for F-fluciclovine PET/MRI to localize recurrent disease. PET/MRI revealed a solitary focus of uptake in a soft tissue nodule in the anterior mediastinum, which was resected and found to be a type B2 thymoma. F-fluciclovine uptake is mediated by amino acid transporters, primarily alanine-serine-cysteine transporter 2 and L-type amino acid transporter 1, previously demonstrated to be expressed on thymic carcinomas. This case highlights the possibility of overexpression of amino acid transporters in thymomas as well, rarely described before.