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Prostate cancer is the commonest non-cutaneous cancer in males and frequently metastasizes to nodal and skeletal tissues. Metastases to soft tissue viscera such as lung and liver are associated with decreased overall survival compared to nodal and skeletal metastases despite androgen deprivation and chemotherapy with palliative intent. We present a case with complete resolution of lung metastases after 225Ac-PSMA targeted alpha endoradiotherapy in a treatment naive patient with metastatic prostate cancer. Our case gives preliminary clinical support for the efficacy of 225Ac-PSMA therapy in lung metastases.

Background A remarkable therapeutic efficacy has been demonstrated with 225Ac-prostate-specific membrane antigen (PSMA)-617 in heavily pre-treated metastatic castration-resistant prostate cancer (mCRPC) patients. We report our experience with 225Ac-PSMA-617 therapy in chemotherapy-naïve patients with advanced metastatic prostate carcinoma. Methods Seventeen patients with advanced prostate cancer were selected for treatment with 225Ac-PSMA-617 in 2-month intervals, with initial activity of 8 MBq, then de-escalation to 7 MBq, 6 MBq or 4 MBq in cases of good response. In one patient, activity was escalated to 13 MBq in the third cycle. Fourteen patients had three treatment cycles administered, while in three patients treatment was discontinued after two cycles due to good response. Six out of 17 patients received additional treatments after the third cycle. Prostate-specific antigen (PSA) was measured every 4 weeks for PSA response assessment. 68Ga-PSMA-PET/CT was used for functional response assessment before each subsequent treatment cycle. Serial full blood count, renal function test, and liver function were obtained to determine treatment-related side effects. Results Good antitumor activity assessed by serum PSA level and 68Ga-PSMA-PET/CT was seen in 16/17 patients. In 14/17 patients, PSA decline ≥90% was seen after treatment, including seven patients with undetectable serum PSA following two (2/7) or three cycles (5/7) cycles of 225Ac-PSMA-617. Fifteen of 17 patients had a > 50% decline in lesions avidity for tracer on 68Ga-PSMA-PET/CT including 11 patients with complete resolution (PET-negative and either stable sclerosis on CT for bone or resolution of lymph node metastases) of all metastatic lesions. Grade 1/2 xerostomia was seen in all patients, and none was severe enough to lead to discontinuation of treatment. One patient had with extensive bone marrow metastases and a background anemia developed a grade 3 anemia while another patient with solitary kidney and pre-treatment grade 3 renal failure developed grade 4 renal toxicity following treatment. The group presented with significant palliation of bone pain and reduced toxicity to salivary glands due to de-escalation. Conclusions 225Ac-PSMA-617 RLT of chemotherapy-naïve patients with advanced metastatic prostate carcinoma led to a ≥ 90% decline in serum PSA in 82% of patients including 41% of patients with undetectable serum PSA who remained in remission 12 months after therapy. The remarkable therapeutic efficacy reported in this study could be achieved with reduced toxicity to salivary glands due to de-escalation of administered activities in subsequent treatment cycles. This necessitates further exploration for informing clinical practice and clinical trial design.

Metastatic prostate carcinoma overexpresses prostate-specific membrane antigen (PSMA), making this antigen a suitable target for radioligand therapy of the disease. Here we report on our experience with a series of 73 castration-resistant prostate carcinoma patients treated with

The author of this article wanted to change the ethical approval statement of the originally published version of this article. Correct statement is indicated below.

The potentially terdentate ligand 1-(S-methyldithio)-3,5-dimethyl-3-(S-methyldithiocarbazato)pyrazoline (H2mdp) was prepared by the reaction of S-methyldithiocarbazate with acetylacetone in an acidic ethanol solution. The neutral complex [TcOCl(mdp)](1) was formed by the reaction of (n-Bu4N)[TcOCl4] with H2mdp in ethanol at room temperature. Compound 1 has a square-pyramidal geometry with the thiolate, thiocarbonyl and amide donor atoms of the terdentate chelate mdp and chloride forming a square plane, with the oxo oxygen in the apical position.

The neutral complex [TcOCl(hdc)] (1) (hdc = S-methyl-β-N-(2-hydroxyphenylethylidene)dithiocarbazate) was prepared by reaction of (n-Bu4N)[TcOCl4] with an equimolar amount of H2hdc in ethanol/dichloromethane at room temperature. With a fourfold mol excess of H2hdc in methanol/acetone, the ‘3 + 2’ complex [TcO(hdc)(adc)] (2) (adc = S-methyl-β-N-(prop-2-ylidene)dithiocarbazate) was isolated. Adc was formed by ketone exchange between solvent acetone and the hydroxyacetophenone fragment of hdc. Compounds 1 and 2 were characterized by infrared spectroscopy, 1H NMR spectrometry, elemental analysis and single-crystal X-ray crystallography. Complex 1 has square-pyramidal geometry with the SNO-donor atoms of the tridentate chelate hdc and chloride forming a square plane, with the oxo oxygen atom in the apical position. Complex 2 has a distorted octahedral geometry, with an S2N2 donor set in the equatorial plane and the oxo and phenolate oxygen atoms in trans apical positions.

The reactions of the ferrocenyl ligands dppf and dfed with [ReO(PPh 3 ) 2 Cl 3 ] afforded the complexes [ReO( dppf - P , P ′)Cl 3 ] ( 1 ), which has a cis – fac arrangement of ligands, and [ReO 2 ( dfed - N , N ′) 2 ] + ( 3 ) ( dppf =1,1′-bis(diphenylphosphino)ferrocene and dfed =bis( N , N ′-ferrocenylmethyl)ethylenediamine). In wet ether, 1 converts into [ReO( dppf - P , P ′)(OH)Cl 2 ] ( 2 ). Crystal structure determinations were performed on 1 and the tetraphenylborate salt of 3 . Compound 1 crystallizes in the orthorhombic system, space group P 2 1 2 1 2 1 with a =11.5364(2), b =15.8381(4) and c =17.5050(4) A and 3 crystallizes in the orthorhombic system, space group Aba 2 with a =15.3773(8), b =15.1344(7) and c =28.2817(14) A.