[μ-N,N,N′,N′-Tetra­kis(2-pyridyl­meth­yl)butane-1,4-diamine]­bis­[dinitratocadmium(II)]

The title dinuclear cadmium complex, [Cd2(NO3)4(C28H32N6)], is located on an inversion center. The unique CdII ion displays a 5 + 2 coordination. A distorted square-pyramidal geometry is formed by the dipicolyl­amine group of the ligand via the N atoms in a meridional fashion and two O atoms of the nitrate ligands with short Cd—O distances. The coordination is completed by two loosely bound O atoms of the nitrate ligands

[μ-N,N,N′,N′-Tetra­kis(2-pyridyl­meth­yl)butane-1,4-diamine]­bis­[dichlorido­copper(II)] trihydrate

The title dinuclear copper complex, [Cu2Cl4(C28H32N6)]·3H2O, is located on a crystallographic inversion center. The unique CuII ion is coordinated in a slightly distorted square-pyramidal environment in which the N atoms of the dipicolyl­amine group and a chloride ligand form the basal plane. The apical position is occupied by a second chloride atom. While the Cu—N distances of the pyridine N atoms are the same within expermental error, the Cu—N distance to the tertiary N atom is slightly elongated. The apical Cu—Cl distance is elongated due to typical Jahn–Teller distortion. One of the water O atoms was refined as disordered over two sites with occupancies 0.734 (17):0.266 (17) and another with half occupancy. H atoms for the disordered solvent atoms were not included in the refinement

[μ-N,N,N′,N′-Tetra­kis­(2-pyridyl­meth­yl)pentane-1,5-diamine]­bis­[dichlorido­copper(II)] sesquihydrate

In the title dinuclear copper complex, [Cu2Cl4(C29H34N6)]·1.5H2O, both CuII ions are coordinated in a slightly distorted square-pyramidal environment in which the N atoms of the dipicolyl­amine group and a chloride ligand form the basal plane. The apical position is occupied by a second chloride atom. The Cu—N distances involving the pyridine N atoms differ slightly from each other and the Cu—N distance involving the tertiary N atom is the longest. The apical Cu—Cl distance is elongated compared to its basal counterpart due to typical Jahn–Teller distortion. In the crystal structure, complex and water mol­ecules are linked via inter­molecular O—H⋯O and O—H⋯Cl hydrogen bonds into chains along [001]. One of the water mol­ecules was refined with half occupancy

[μ-N,N,N′,N′-Tetra­kis(2-pyridyl­meth­yl)butane-1,4-diamine]­bis­[diacetato­cadmium(II)] nona­hydrate

The title dinuclear complex, [Cd2(CH3CO2)4(C28H32N6)]·9H2O, is located on a crystallographic inversion center. The unique CdII ion displays a 5 + 2 coordination. A distorted square-pyramidal geometry is formed by the dipicolyl­amine unit of the ligand via the N atoms in a meridional fashion and two O atoms of the acetate ligands with short Cd—O distances. The coordination is completed by two loosely bound O atoms of the acetate ligands. The Cd—N distances involving the pyridine N atoms differ slightly from each other and the Cd—N distance involving the tertiary N atom is the longest. In the crystal structure, complex mol­ecules and solvent water mol­ecules are connected into a three-dimensional network via inter­molecular O—H⋯O hydrogen bonds. One of the water mol­ecules lies on a twofold rotation axis

[μ-N,N,N′,N′-Tetra­kis(2-pyridyl­meth­yl)butane-1,4-diamine]­bis­[dibromidocopper(II)]

The title dinuclear copper complex, [Cu2Br4(C28H32N6)], is located on an inversion center. The unique CuII ion is in a slightly distorted square-pyramidal environment in which the N atoms of a dipicolyl­amine group and a bromide ligand form the basal plane. The apical site is occupied by a second Br atom. While the Cu—N distances involving the pyridine N atoms are the same within experimental error, the Cu—N distance involving the tertiary N atom is slightly elongated. Due to the typical Jahn–Teller distortion of copper(II) complexes, the apical Cu—Br distance is elongated

2-(1,3-Dioxoisoindolin-2-yl)ethyl 4-methyl­benzene­sulfonate

In the title mol­ecule, C17H15NO5S, the dihedral angle between the essentially planar atoms of the tosyl moiety (the S atom and the seven tolyl C atoms) and the phthalimide moiety is 6.089 (3)°. The mol­ecule is folded about the ethyl­ene bridge, adopting a staggered conformation such that the benzene ring of the tosyl group and the five-membered ring of the phthalimide moiety have a face-to-face orientation with a centroid-to-centroid separation of 3.7454 (12) Å. The crystal structure is stabilized by weak inter­molecular π–π inter­actions between symmetry-related five-membered rings of the phthalimide groups, with a centroid-to-centroid distance of 3.3867 (11) Å. The compound is used for the attachment of a suitable chelate functionality for radiolabeling purposes

1-(Phthalimidometh­yl)pyridinium p-toluene­sulfonate

In the crystal of the title compound, C14H11N2O2 +·C7H7O3S−, the cation and anion inter­act by way of an aromatic π–π inter­action [centroid–centroid separation = 3.5783 (2) Å] and a T-stacking (C—H⋯π) inter­action between cations. The dihedral angle between the aromatic rings in the cation is 61.73 (8)°. The ionic units are aligned in a zigzag fashion in the b-axis direction

Renal Safety of [177Lu]Lu-PSMA-617 Radioligand Therapy in Patients with Compromised Baseline Kidney Function

Background: Radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) is an effective antitumor-treatment in metastatic castration-resistant prostate carcinoma (mCRPC). Concerns of potential nephrotoxicity are based on renal tubular PSMA expression and the resulting radiopharmaceutical retention during RLT, but data confirming clinically significant renal toxicity are still lacking. In this study, patients with significantly impaired baseline kidney function before initiation of therapy were investigated for treatment-associated nephrotoxicity and the potential relationship with administered activities of [177Lu]Lu-PSMA-617. Methods: Twenty-two mCRPC patients with impaired renal function (glomerular filtration rate (GFR) ≤ 60 mL/min) who received more than two cycles of [177Lu]Lu-PSMA-617 RLT (median 5 cycles and median 6-week time interval between consecutive cycles) were analyzed in this study. Patients were treated within a prospective patient registry (REALITY Study, NCT04833517). Cumulative administered activities ranged from 17.1 to 85.6 GBq with a median activity of 6.5 GBq per cycle. Renal function was closely monitored during and after PSMA-RLT. Results: Mean pre-treatment GFR was 45.0 ± 10.7 mL/min. After two (22/22 patients), four (20/22 patients), and six cycles (10/22 patients) of RLT, a significant increase of GFR was noted (each p < 0.05). End-of-treatment GFR (54.1 ± 16.7 mL/min) was significantly higher than baseline GFR (p = 0.016). Only one patient experienced deterioration of renal function (change of CTCAE grade 2 to 3). The remaining patients showed no significant reduction of GFR, including follow-up assessments (6, 9, and 12 months), and even showed improved (10/22 patients) or unchanged (11/22 patients) CTCAE-based renal impairment grades during and after the end of PSMA-RLT. No significant correlation between the change in GFR and per-cycle (p = 0.605) or cumulative (p = 0.132) administered activities were found. Conclusions: As pre-treatment chronic kidney failure did not lead to detectable RLT-induced deterioration of renal function in our study, the nephrotoxic potential of [177Lu]Lu-PSMA-617 RLT may be overestimated and not of clinical priority in the setting of palliative treatment in mCRPC. We suggest not to categorically exclude patients from enrolment to PSMA-RLT due to renal impairment

Molecular imaging and biochemical response assessment after a single cycle of [225Ac]Ac-PSMA-617/[177Lu]Lu-PSMA-617 tandem therapy in mCRPC patients who have progressed on [177Lu]Lu-PSMA-617 monotherapy

Rationale: Despite the promising results of prostate-specific membrane antigen (PSMA)-targeted 177Lu radioligand therapy in metastatic castration-resistant prostate carcinoma (mCRPC), some patients do not respond and other patients with initially good response develop resistance to this treatment. In this study, we investigated molecular imaging and biochemical responses after a single cycle of [225Ac]Ac-PSMA-617/[177Lu]Lu-PSMA-617 tandem therapy in patients who had progressed on [177Lu]Lu-PSMA-617 monotherapy. Methods: Seventeen patients with mCRPC were included in a retrospective, monocenter study. Molecular imaging-based response was assessed by modified PERCIST criteria using the whole-body total lesion PSMA (TLP) and molecular tumour volume (MTV) derived from [68Ga]Ga-PSMA-11 PET/CT. Biochemical response was evaluated according to PCWG3 criteria using the prostate-specific antigen (PSA) serum value. Concordance and correlation statistics as well as survival analyses were performed. Results: Based on the molecular imaging-based response assessment, 5 (29.4%) patients showed partial remission and 7 (41.2%) had stable disease. The remaining 5 (29.4%) patients had further progression, four with an increase in TLP/MTV of >30% and one with stable TLP/MTV but appearance of new metastases. Based on the biochemical response assessment, 5 (29.4%), 8 (47.1%), and 4 (23.5%) patients showed partial remission, stable disease, and progressive disease, respectively. A comparison of the response assessment methods showed a concordance of 100% (17/17) between TLP and MTV and 70.6% (12/17) between TLP/MTV and PSA. Patients with partial remission, independently assessed by each method, had better overall survival (OS) than patients with either stable or progressive disease. The difference in OS was statistically significant for the molecular imaging response assessment (median OS not reached vs. 8.3 m, p = 0.044), but not for the biochemical response assessment (median OS 18.1 m vs. 9.4 m, p = 0.468). Conclusion: Based on both assessment methods, [225Ac]Ac-PSMA-617/[177Lu]Lu-PSMA-617 tandem therapy is an effective treatment for the highly challenging cohort of patients with mCRPC who have progressed on [177Lu]Lu-PSMA-617 monotherapy. Molecular imaging response and biochemical PSA response were mostly concordant, though a considerable number of cases (29.4%) were discordant. Molecular imaging response reflecting the change in total viable tumour burden appears to be superior to PSA change in estimating survival outcome after tandem therapy

Addition of Standard Enzalutamide Medication Shows Synergistic Effects on Response to [177Lu]Lu-PSMA-617 Radioligand Therapy in mCRPC Patients with Imminent Treatment Failure—Preliminary Evidence of Pilot Experience

Well-received strong efficacy of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) does not prevent patients from either early or eventual disease progression under this treatment. In this study, we investigated co-medication with enzalutamide as a potential re-sensitizer for PSMA-RLT in patients with imminent treatment failure on standard 177Lu-based PSMA-RLT. Ten mCRPC patients who exhibited an insufficient response to conventional [177Lu]Lu PSMA-617 RLT received oral medication of enzalutamide 160 mg/d as an adjunct to continued PSMA RLT. Prostate-specific antigen (PSA) and standard toxicity screening lab work-up were performed to assess the treatment efficacy and safety in these individuals. The mean PSA increase under PSMA-RLT before starting the re-sensitizing procedure was 22.4 ± 26.5%. After the introduction of enzalutamide medication, all patients experienced a PSA decrease, –43.4 ± 20.0% and –48.2 ± 39.0%, after one and two cycles of enzalutamide-augmented PSMA-RLT, respectively. A total of 70% of patients (7/10) experienced partial remission, with a median best PSA response of –62%. Moreover, 5/6 enzalutamide-naïve patients and 2/4 patients who had previously failed enzalutamide exhibited a partial remission. There was no relevant enzalutamide-induced toxicity observed in this small cohort. This pilot experience suggests the synergistic potential of adding enzalutamide to PSMA-RLT derived from the intra-individual comparison of 177Lu-based PSMA-RLT ± enzalutamide