Radiolabeled Somatostatin Receptor Antagonist Versus Agonist for Peptide Receptor Radionuclide Therapy in Patients with Therapy-Resistant Meningioma: PROMENADE Phase 0 Study.

Our primary aim was to compare the therapeutic index (tumor-to-bone marrow and tumor-to-kidney absorbed-dose ratios) of the new radiolabeled somatostatin receptor antagonist [177Lu]Lu-DOTA-JR11 with the established radiolabeled somatostatin receptor agonist [177Lu]Lu-DOTATOC in the same patients with progressive, standard therapy-refractory meningioma. Methods: In this prospective, single-center, open-label phase 0 study (NCT04997317), 6 consecutive patients were included: 3 men and 3 women (mean age, 63.5 y). Patients received 6.9-7.3 GBq (standard injected radioactivity) of [177Lu]Lu-DOTATOC followed by 3.3-4.9 GBq (2 GBq/m2 × body surface area) of [177Lu]Lu-DOTA-JR11 at an interval of 10 ± 1 wk. In total, 1 [177Lu]Lu-DOTATOC and 2-3 [177Lu]Lu-DOTA-JR11 treatment cycles were performed. Quantitative SPECT/CT was done at approximately 24, 48, and 168 h after injection of both radiopharmaceuticals to calculate meningioma and organ absorbed doses as well as tumor-to-organ absorbed-dose ratios (3-dimensional segmentation approach for meningioma, kidneys, liver, bone marrow, and spleen). Results: The median of the meningioma absorbed dose of 1 treatment cycle was 3.4 Gy (range, 0.8-10.2 Gy) for [177Lu]Lu-DOTATOC and 11.5 Gy (range, 4.7-22.7 Gy) for [177Lu]Lu-DOTA-JR11. The median bone marrow and kidney absorbed doses after 1 treatment cycle were 0.11 Gy (range, 0.05-0.17 Gy) and 2.7 Gy (range, 1.3-5.3 Gy) for [177Lu]Lu-DOTATOC and 0.29 Gy (range, 0.16-0.39 Gy) and 3.3 Gy (range, 1.6-5.9 Gy) for [177Lu]Lu-DOTA-JR11, resulting in a 1.4 (range, 0.9-1.9) times higher median tumor-to-bone marrow absorbed-dose ratio and a 2.9 (range, 2.0-4.8) times higher median tumor-to-kidney absorbed-dose ratio with [177Lu]Lu-DOTA-JR11. According to the Common Terminology Criteria for Adverse Events version 5.0, 2 patients developed reversible grade 2 lymphopenia after 1 cycle of [177Lu]Lu-DOTATOC. Afterward, 2 patients developed reversible grade 3 lymphopenia and 1 patient developed reversible grade 3 lymphopenia and neutropenia after 2-3 cycles of [177Lu]Lu-DOTA-JR11. No grade 4 or 5 adverse events were observed at 15 mo or more after the start of therapy. The disease control rate was 83% (95% CI, 53%-100%) at 12 mo or more after inclusion. Conclusion: Treatment with 1 cycle of [177Lu]Lu-DOTA-JR11 showed 2.2-5.7 times higher meningioma absorbed doses and a favorable therapeutic index compared with [177Lu]Lu-DOTATOC after injection of 1.4-2.1 times lower activities. The first efficacy results demonstrated a high disease control rate with an acceptable safety profile in the standard therapy for refractory meningioma patients. Therefore, larger studies with [177Lu]Lu-DOTA-JR11 are warranted in meningioma patients.

Relation of Low-Density Lipoprotein Cholesterol With Microvascular Injury and Clinical Outcome in Revascularized ST-Elevation Myocardial Infarction.

BACKGROUND: Microvascular injury (MVI) after primary percutaneous coronary intervention for ST-elevation myocardial infarction (STEMI) is a major determinant of adverse clinical outcome. Experimental data indicate an impact of hypercholesterolemia on MVI; however, there is a lack of clinical studies confirming this relation. We aimed to investigate the association of cholesterol concentrations on admission with MVI visualized by cardiac magnetic resonance imaging and clinical outcome in STEMI patients treated by primary percutaneous coronary intervention. METHODS AND RESULTS: In this prospective, observational study, we included 235 consecutive revascularized STEMI patients. Cholesterol (total cholesterol, low-density lipoprotein [LDL], and high-density lipoprotein cholesterol) and triglyceride concentrations were determined at presentation. Cardiac magnetic resonance scans were performed 2 (2-4) days after infarction to assess infarct characteristics, including MVI. Clinical end point was the occurrence of major adverse cardiac events (MACE) comprising all-cause mortality, nonfatal reinfarction, and new congestive heart failure. Patients with MVI (n=129; 55%) showed higher levels of total cholesterol (204 [172-226] versus 185 [168-212] mg/dL; P=0.01) and LDL cholesterol (142 [113-166] versus 118 [103-149] mg/dL; P=0.001), whereas high-density lipoprotein cholesterol and triglycerides did not differ significantly. In multivariable analysis, including all significant clinical and cardiac magnetic resonance determinants of MVI, LDL concentration emerged as an independent predictor of MVI (odds ratio, 1.02 [95% confidence interval, 1.01-1.02]; P=0.002). Furthermore, increased LDL cholesterol (>150 mg/dL) significantly predicted the occurrence of major adverse cardiac events (hazard ratio, 3.09 [95% confidence interval, 1.22-7.87]; P=0.01). CONCLUSIONS: In STEMI patients undergoing primary percutaneous coronary intervention, baseline LDL cholesterol concentrations were independently associated with MVI, revealing a clinically relevant link between LDL metabolism and MVI in acute STEMI.