64Cu-SAR-bisPSMA (PROPELLER) positron emission tomography (PET) imaging in patients with confirmed prostate cancer.

person Eva Lengyelova Clarity Pharmaceuticals, Eveleigh, NSW, Australia info_outline Eva Lengyelova, Veronica Wong, Nat Lenzo, Michelle Parker, Louise Emmett

Authors person Eva Lengyelova Clarity Pharmaceuticals, Eveleigh, NSW, Australia info_outline Eva Lengyelova, Veronica Wong, Nat Lenzo, Michelle Parker, Louise Emmett Organizations Clarity Pharmaceuticals, Eveleigh, NSW, Australia, Nepean Hospital, Sydney, NSW, Australia, Genesiscare, East Fremantle, NSW, Australia, Department of Theranostics and Nuclear Medicine, St Vincent's Hospital; Faculty of Medicine, UNSW, Sydney, NSW, Australia Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Calrity Pharmaceuticals Background: Prostate cancer (PC) is the second most frequent malignancy in men globally. Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein that is overexpressed in PC. Recently, several new 68 Ga- and 18 F-based PSMA-targeted PET agents have been approved by the FDA to detect PC, which offer improved sensitivity and specificity compared to traditional imaging. Methods: PROPELLER (NCT04839367) investigated 64 Cu-SAR-bisPSMA in 30 men with untreated, histopathologically proven, primary PC with intermediate- to high-risk features. At screening, patients completed 68 Ga-PSMA-11 PET/CT at 1h post dose. Following enrollment, patients received either 100MBq, 150MBq or 200MBq of 64 Cu-SAR-bisPSMA, followed by PET/CT at 2-4h post dose. Safety was evaluated before and after 64 Cu-SAR-bisPSMA dosing. The 68 Ga-PSMA-11 and 64 Cu-SAR-bisPSMA PET/CT scans were evaluated by 2 independent, blinded central readers for image quality, PC detection, and intensity of tracer uptake in lesions (SUVmax and Tumor-to-Background Ratio [TBR]). Results: A single, Grade 1 64 Cu-SAR-bisPSMA-related AE was reported in the 200MBq cohort. Both readers scored 200MBq of 64 Cu-SAR-bisPSMA as the dose providing the highest image quality. In this cohort, 64 Cu-SAR-bisPSMA and 68 Ga-PSMA-11 was able to detect primary PC in 100% and 77.8% of patients for Reader 1 and 85.7% and 83.3% of patients for Reader 2, respectively. In the 200MBq cohort, Reader 1 identified 41 lesions with 64 Cu-SAR-bisPSMA vs 36 lesions with 68 Ga-PSMA-11, while Reader 2 identified 31 lesions with 64 Cu-SAR-bisPSMA vs 22 lesions with 68 Ga-PSMA-11. In the 200MBq cohort, 64 Cu-SAR-bisPSMA consistently showed higher uptake compared to 68 Ga-PSMA-11 (SUVmax: Reader 1 median [IQR]: 31.40 [27.45] vs 10.08 [13.92], p < 0.001, Reader 2 median [IQR]: 41.00 [46.09] vs 14.58 [14.98], p < 0.001); TBR: Reader 1 median [IQR]: 49.07 [67.69] vs 21.91 [35.71], P = 0.0015), Reader 2 median [IQR]: 76.34 [66.37] vs 23.90 [33.05], p < 0.001). Conclusions: 64 Cu-SAR-bisPSMA was safe and effective for detecting PSMA-expressing lesions. 200 MBq of 64 Cu-SAR-bisPSMA was determined as the optimal dose for future trials. 64 Cu-SAR-bisPSMA PET/CT showed a greater number of lesions and lesions exhibited significantly higher uptake when compared to 68 Ga-PSMA-11 in men being with intermediate- to high-risk PC. Further studies to evaluate 64 Cu-SAR-bisPSMA as an imaging agent in patients with biochemical recurrence of PC are underway. Clinical trial information: NCT04839367.

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