Lantheus Medical Imaging (United States)

Amyloid PET imaging enables the in vivo visualization and quantification of amyloid-beta deposits in the brain. In research and clinical settings, it is further used to monitor amyloid-beta burden as well as the biological response to disease-modifying therapies. Amyloid-beta targeting monoclonal antibodies (mAbs) such as lecanemab and donanemab were designed to reduce brain amyloid-beta burden. If the PET tracer and the mAbs would bind to the same site, the PET signal may be impacted in patients undergoing therapy. Binding interaction studies were conducted to verify the reliability of PET readouts in this setting. The aim of this study was to investigate whether lecanemab or donanemab interfere with the binding of the amyloid PET tracer florbetaben to aggregated amyloid-beta deposits in vitro. Human Alzheimer’s disease (AD) brain tissue from various sources was used to assess potential interactions between florbetaben and lecanemab or donanemab. Three complementary approaches were used to confirm target binding and to study potential interactions: (1) competitive immunohistochemistry (IHC), (2) competitive autoradiography (ARG), and (3) ligand binding assays (LBA). Across all three sets of experiments, no evidence of competition or inhibition of florbetaben binding to amyloid-beta deposits by lecanemab or donanemab was observed. Autoradiography demonstrated robust tracer binding to amyloid-beta plaques that was unaffected by incubation with excess antibody. Similarly, IHC and LBA experiments confirmed that florbetaben and the tested mAbs target distinct binding sites on amyloid-beta aggregates. These results demonstrate that neither lecanemab nor donanemab interfere with florbetaben binding to amyloid-beta plaques in vitro, further validating its use in this setting. While the current data are limited to in-vitro experiments, they further support the use of florbetaben PET for monitoring amyloid-beta changes during treatment with amyloid-beta targeting therapies.

Fibroblast activation protein-expressing (FAP+) fibroblasts are central mediators of cardiac remodeling after injury or disease. The aim of this study was to evaluate a new PET tracer, 64Cu-LNTH-1363S, to detect FAP+ fibroblasts in myocardial infarction (MI) mouse models. Methods: The permanent left anterior descending coronary artery ligation and the echocardiography-guided ischemia reperfusion models were used to assess the targeting efficiency of 64Cu-LNTH-1363S. Competitive receptor blocking and autoradiography studies were performed to confirm the invivo targeting specificity. Results: 64Cu-LNTH-1363S demonstrated sensitive and specific detection of FAP+ cells in the 2 MI models. Kinetic modeling data showed that the distribution volume was higher in the infarct zone than in the remote myocardium. Conclusion: This study establishes the feasibility of 64Cu-LNTH-1363S for noninvasive detection of FAP+ fibroblasts in MI mouse models and provides preclinical data to support further investigation of this process in humans after various forms of cardiac injury.

PERLA is a global, double-blind, parallel phase II trial (NCT04581824) comparing efficacy and safety of anti–PD-1 antibodies dostarlimab and pembrolizumab, plus chemotherapy (DCT and PCT, respectively) as first-line treatment in patients with metastatic non-squamous NSCLC without known targetable genomic aberrations. Patients stratified by PD-L1 tumor proportion score and smoking status were randomized 1:1, receiving ≤35 cycles 500 mg dostarlimab or 200 mg pembrolizumab, ≤35 cycles 500 mg/m2 pemetrexed and ≤4 cycles cisplatin (75 mg/m2) or carboplatin (AUC 5 mg/ml/min) Q3W. Primary endpoint was overall response rate (ORR) (blinded independent central review). Secondary endpoints include progression-free survival (PFS) based on investigator assessment, overall survival (OS) and safety. Exploratory endpoints include ORR by PD-L1 subgroup and duration of response. PERLA met its pre-specified endpoint. ORR (n/N; 95% CI) is 45% (55/121; 36.4–54.8) for DCT and 39% (48/122; 30.6–48.6) for PCT (data cut-off: 07 July 23), numerically favoring dostarlimab in PD-L1-positive subgroups. Median PFS (months [95% CI]) is 8.8 (6.7–10.4) for DCT and 6.7 (4.9–7.1) for PCT (HR 0.70 [95% CI: 0.50–0.98]; data cut-off: 04 August 22). Median OS (months [95% CI]) is 19.4 (14.5–NR) for DCT and 15.9 (11.6–19.3) for PCT (HR 0.75 [95% CI: 0.53–1.05]) (data cut-off: 07 July 23). Safety profiles are similar between groups. In this study, DCT shows similar efficacy to PCT and demonstrates clinical efficacy as first-line treatment for patients with metastatic non-squamous NSCLC.

61 Background: Piflufolastat F 18 is a PSMA-targeted radiopharmaceutical approved in the US for imaging prostate cancer (PCa) patients both at the time of initial staging and at disease recurrence. In a phase 3 study of patients with biochemically recurrent (BCR) PCa, we reported that nearly two-thirds (63.9%; 131/205) of participants had a change in their intended disease management plan based on pre- and post-piflulfolastat F 18 PET/CT management questionnaires (MMQs) completed by the treating physicians. The clinical utility of piflufolastat F 18 scanning in men with very low/low PSA levels (<0.5 ng/mL) and a detection rate of ~36% has not been previously described. Here we report the changes in intended management in this subset of patients. Methods: Men ≥18 years of age with a rising PSA after definitive PCa therapy and negative or equivocal imaging were enrolled. A single ~9 mCi (333 MBq) dose of piflufolastat F 18 was administered followed by PET/CT from mid-thigh through skull vertex 1-2 hours later. Prior to scanning, the treating physicians completed a pre-PET MMQ to document the initial intended management plan for their patients based on available clinical information including baseline conventional imaging results. After PET, they completed a post-PET MMQ and recorded the management plan in light of PET findings. Treatment recommendations that differed from the pre-scan recommendations were reported as changes in the intended management plan. Results: 208 men (median PSA 0.8 ng/mL [range 0.17-98.45], n=202) underwent piflufolastat F 18-PET/CT. 200 evaluable patients had both a baseline PSA value and completed MMQs. Of 131 patients with a recorded change in intended management, 127 had an evaluable baseline PSA level. Of the 69 patients with baseline PSA levels ≤0.5ng/mL, 27 (39.1%) recorded a change in intended disease management based on positive (n=20) or negative (n=7) PET, including salvage local to systemic therapy (n=15); systemic to local therapy (n=3); observation to treatment (n=5); and treatment to observation (n=4). An additional 15 patients (21.7%) had recommended bidirectional change in management (e.g., salvage RT+ADT) and are excluded in this report. Specific treatment intensification/de-intensification plans are under investigation. Conclusions: The frequency of changes in intended disease management observed in BCR PCa patients with low baseline PSA levels (≤0.5ng/mL) was 39.1%. Both negative and positive PET/CT results impacted treatment recommendations and can provide useful and actionable information. Clinical trial information: NCT02981368 .

To measure the performance of multiparametric (mp) magnetic resonance imaging (MRI) to identify intraprostatic tumour deposits using a systematic and targeted MR-guided transperineal prostate biopsy technique. Patients underwent a combined systematic and targeted MR-guided transperineal biopsy procedure in the dorsal lithotomy position under general anaesthesia. Systematic biopsies were spaced 10 mm or less apart and additional biopsies targeted any Prostate Imaging-Reporting and Data System (PI-RADS) 3, 4 or 5 lesions identified on mpMRI. Cancer detection rates were calculated on a per patient and per lesion basis. A total of 125 patients underwent the biopsy procedure. The positive predictive value (PPV) of mpMRI per patient was 59% for any cancer and 49% for Gleason score (GS) ≥ 7 cancer. The negative predictive value (NPV) of mpMRI per patient was 67% for any cancer and 88% for GS ≥ 7 cancer. On a per lesion basis, the PPV of PI-RADS 3 lesions for any and GS ≥ 7 cancer was 24% and 10%. For PI-RADS 4 lesions it was 42% and 32%. For PI-RADS 5 lesions, it was 76% and 70%. MpMRI failed to identify GS ≥ 7 cancer found on systematic biopsy in 22% of patients. Based on a combination of systematic and targeted transperineal prostate biopsies, mpMRI showed a high NPV and low PPV for GS ≥ 7 cancer on a per patient basis. The PPV of mpMRI on a per lesion basis increased with increasing PI-RADS score. However, there were a significant number of both false positive as well as false negative (mpMRI invisible) areas within the prostate that contained GS ≥ 7 cancer. Therefore, pathologic confirmation using both targeted and systematic mapping biopsy is necessary to accurately identify all intraprostatic tumour deposits.