Gary A. Ulaner

In participants with multiple myeloma, CD38-targeted zirconium 89 deferoxamine-daratumumab immuno-PET/CT helped detect active myeloma, even in some participants with no signs of disease at fluorine 18 fluorodeoxyglucose PET/CT.

A 67-year-old man with melanoma underwent FDG PET/CT demonstrating FDG-avid curvilinear soft tissue anterior, lateral, and posterior to the left kidney. This soft tissue structure is Gerota fascia, a fibrous sheath encasing the kidneys, adrenal glands, and adjacent fat, which protects these structures from trauma and is a barrier to the spread of hemorrhage and infection. This case demonstrates an important anatomic structure not commonly visualized on FDG PET/CT, identified here due to involvement with malignancy. Physicians interpreting FDG PET/CT should be aware of the location and function of Gerota fascia, as well as its appearance when pathologically involved.

PURPOSE: Many patients with ER-positive HER2-negative metastatic breast cancer (MBC) derive limited benefit from second line endocrine therapy. This study evaluated the impact of [18F]fluoroestradiol (FES) PET/CT on second line therapeutic decision-making.METHODS: Patients with progression of ER-positive HER2-negative MBC on first line endocrine therapy were prospectively enrolled in 17 U.S. centers to undergo [18F]FES PET/CT after standard-of-care (SoC) imaging. [18F]FES uptake in MBC lesions was evaluated. Treating oncologists completed questionnaires before and after [18F]FES PET/CT, detailing therapeutic decisions plus their confidence in the decisions. The primary endpoint was the proportion of patients whose therapeutic management changed after [18F]FES PET/CT.RESULTS: Between January 2023 and May 2024, 45 patients underwent [18F]FES PET/CT. Imaging results led to management changes in 17 patients (37.8%; 95% CI 23.8% - 53.5%). Twenty-five patients avoided further diagnostic testing, while 7 patients received additional tests. Oncologist’s confidence in second line treatment decision increased on average from 6.6 before [18F]FES PET/CT to 8.6 afterward on a ten-point scale (p <0.0001). In 25 patients (55.6%), lesions visible on SoC imaging were reported as “absent” (FES-negative) on [18F]FES PET/CT, suggesting potential loss or downregulation of ER that functionally binds estrogen.CONCLUSION: [18F]FES PET/CT altered therapeutic management in 37.8% of patients with MBC progressing on first line endocrine therapy and significantly increased oncologist’s confidence in treatment selection. This imaging modality could help prevent unnecessary prolongation of ineffective endocrine therapy and delays in initiation of more effective options. Future studies should investigate potential outcome benefits after [18F]FES PET/CT-informed management changes.

Higher liver background uptake was observed on prostate-specific membrane antigen (PSMA)–targeted PET imaging with fluorine 18 ( ¹⁸ F)-flotufolastat and ¹⁸ F-PSMA-1007 compared with ¹⁸ F-piflufolastat and gallium 68 ( ⁶⁸ Ga)-PSMA-11, which may influence patient eligibility for PSMA-targeted therapy.

Demographic and Baseline characteristics of the Safety Population

Treatment-Emergent Adverse Events

Summary of Subject Disposition (All subjects)

Subgroup Analyses of PSA50 Response

Purpose:The phase II ARROW study was designed to evaluate radioligand therapy (RLT) with 131I-LNTH-1095, an iodine-131–labeled small molecule targeting prostate-specific membrane antigen (PSMA), in combination with enzalutamide in subjects with metastatic castration-resistant prostate cancer after progression on prior abiraterone therapy.Patients and Methods:Men ≥18 years with PSMA-positive prostate cancer (PSMA PET tracer uptake >1× liver SUVmean in all CT-measurable lesions) were randomly assigned 2:1 to 131I-LNTH-1095 (4 cycles of 3.7 GBq/dose every 8 weeks) + enzalutamide (160 mg orally once daily) versus enzalutamide alone. The primary endpoint was PSA50 response. Secondary endpoints included radiographic progression-free survival (rPFS), objective response rate, overall survival (OS), and safety.Results:Of 177 screened subjects, 120 were randomly assigned (80: 131I-LNTH-1095 + enzalutamide; 40: enzalutamide monotherapy). PSA50 response was 62.9% [95% confidence interval (CI), 50.5–74.1] for 131I-LNTH-1095 + enzalutamide versus 31.3% (16.1–50) for enzalutamide alone (P = 0.003). The median rPFS was 14.0 months (95% CI, 8.64–18.20) for 131I-LNTH-1095 + enzalutamide versus 11.5 months (2.79–18.43) for enzalutamide alone (P = 0.10). The incidence of grade ≥3 treatment-emergent adverse events (TEAE) was 65.8% for 131I-LNTH-1095 + enzalutamide versus 41% for enzalutamide monotherapy; the most frequent TEAEs were fatigue (75% vs. 53.8%), nausea (59.2% vs. 33.3%), thrombocytopenia (51.3% vs. 0%), and decreased appetite (48.7% vs. 17.9%), respectively. Two deaths in the 131I-LNTH-1095 + enzalutamide group were considered treatment-related. The study was not powered to detect rPFS and OS differences.Conclusions:131I-LNTH-1095 + enzalutamide was associated with a statistically significant improvement in PSA50 response compared with enzalutamide alone despite a lower dosing schedule (4 cycles of 3.7 GBq/dose every 8 weeks) than the other approved PSMA RLT agents. Grade ≥3 adverse events were more frequent with combination therapy, particularly hematologic toxicity.