ABSTRACT
Approaches to developing large-scale superconducting quantum processors must cope with the numerous microscopic degrees of freedom that are ubiquitous in solid-state devices. State-of-the-art superconducting qubits employ aluminium oxide (AlOx) tunnel Josephson junctions as the sources of nonlinearity necessary to perform quantum operations. Analyses of these junctions typically assume an idealized, purely sinusoidal current-phase relation. However, this relation is expected to hold only in the limit of vanishingly low-transparency channels in the AlOx barrier. Here we show that the standard current-phase relation fails to accurately describe the energy spectra of transmon artificial atoms across various samples and laboratories. Instead, a mesoscopic model of tunnelling through an inhomogeneous AlOx barrier predicts percent-level contributions from higher Josephson harmonics. By including these in the transmon Hamiltonian, we obtain orders of magnitude better agreement between the computed and measured energy spectra. The presence and impact of Josephson harmonics has important implications for developing AlOx-based quantum technologies including quantum computers and parametric amplifiers. As an example, we show that engineered Josephson harmonics can reduce the charge dispersion and associated errors in transmon qubits by an order of magnitude while preserving their anharmonicity.
ABSTRACT
The use of 225Ac in prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), either as monotherapy or in combination with 177Lu, is a promising therapy approach in patients with metastatic castration-resistant prostate carcinoma (mCRPC). In this study, we report the efficacy and safety of [225Ac]Ac-PSMA-617 augmented [177Lu]Lu-PSMA-617 RLT in 177Lu-naive mCRPC patients (n = 15) with poor prognosis (presence of visceral metastases, high total tumor burden with diffuse bone metastases or a short PSA doubling time of <2 months). Biochemical (by PSA serum value) and molecular imaging response (by [68Ga]Ga-PSMA-11 PET/CT) was assessed after two cycles of [177Lu]Lu-PSMA-617 RLT, with at least one [225Ac]Ac-PSMA-617 augmentation. In addition, PSA-based progression-free survival (PSA-PFS), overall survival (OS) and toxicity (according to CTCAE) were analyzed. We observed a biochemical- and molecular imaging-based partial remission in 53.3% (8/15) and 66.7% (10/15) of patients, respectively. The median PSA-PFS and OS was 9.1 and 14.8 months, respectively. No serious acute adverse events were recorded. Two out of fifteen patients experienced grade 3 anemia. No other grade 3/4 toxicities were observed. RLT-related xerostomia (grade 1/2) was recorded in 2/15 patients. Our data showed a high clinical efficacy with a favorable side effects profile of [225Ac]Ac-PSMA-617 augmented [177Lu]Lu-PSMA-617 RLT in this highly challenging patient cohort.
