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Nonmelanoma skin cancer and its treatment represent a significant global cancer burden for health care systems and patients. Rhenium skin cancer therapy (Rhenium SCT) is a novel noninvasive radionuclide nonmelanoma skin cancer treatment, which can be provided in a single outpatient session. The aim of this prospective, multicenter, single-arm, international, phase IV study (EPIC-Skin) is to assess clinic- and patient-reported outcomes of Rhenium SCT as a treatment for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Methods: Eligible patients had biopsy-proven stage I or stage II BCC or SCC lesions no more than 3 mm deep and no larger than 8 cm 2 in area. Rhenium SCT resin was applied to an adhesive foil affixed to the target lesion in a single session. Interim efficacy and safety analysis were planned once 50% of target patients had recorded a 6-mo follow-up visit. Primary outcome is the proportion of lesions achieving complete response using modified RECIST. Secondary and other outcome measures include patient-reported quality of life (QoL), treatment comfort, and cosmesis. Results: A total of 182 patients was enrolled and administered Rhenium SCT (50 Gy dose to deepest point of target) to at least 1 BCC or SCC. Of 81 patients who reached the 6-mo posttreatment follow-up, it was found that 97.2% (103/106) of lesions showed complete responses and 2.8% (3/106) had partial responses. Improvements in QoL were also reported, whereas no patients reported any pain or discomfort during treatment. Adverse events were reported in 15.9% (29/182) of patients and were rated grade 1 ( n = 19), grade 2 ( n = 9), or grade 3 ( n = 1). Conclusion: This preliminary analysis of the EPIC-Skin study indicates that Rhenium SCT is safe and effective for the treatment of BCC and SCC and is associated with significant QoL improvements. It will be particularly beneficial for lesions that are difficult to treat surgically because of size and location. It is also beneficial for patients with comorbidities or those unable to receive conventional fractionated radiotherapy., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Actinium-225 ( 225 Ac) prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) is a novel therapy for metastatic castration-resistant prostate cancer (mCRPC). We aimed to report the safety and antitumour activity of 225 Ac-PSMA RLT of mCRPC in a large cohort of patients treated at multiple centres across the world., Methods: This retrospective study included patients treated at seven centres in Australia, India, Germany, and South Africa. We pooled data of consecutive patients of any age and Eastern Cooperative Oncology Group performance status with histopathologically confirmed adenocarcinoma of the prostate who were treated with one or more cycles of 8 MBq 225 Ac-PSMA RLT administered intravenously for mCRPC. Previous lines of mCRPC treatment included taxane-based chemotherapy, androgen-receptor-axis inhibitors, lutetium-177 ( 177 Lu) PSMA RLT, and radium-223 dichloride. The primary outcomes were overall survival and progression-free survival., Findings: Between Jan 1, 2016, and May 31, 2023, 488 men with mCRPC received 1174 cycles of 225 Ac-PSMA RLT (median two cycles, IQR 2-4). The mean age of the patients was 68·1 years (SD 8·8), and the median baseline prostate-specific antigen was 169·5 ng/mL (IQR 34·6-519·8). Previous lines of treatment were docetaxel in 324 (66%) patients, cabazitaxel in 103 (21%) patients, abiraterone in 191 (39%) patients, enzalutamide in 188 (39%) patients, 177 Lu-PSMA RLT in 154 (32%) patients, and radium-223 dichloride in 18 (4%) patients. The median follow-up duration was 9·0 months (IQR 5·0-17·5). The median overall survival was 15·5 months (95% CI 13·4-18·3) and median progression-free survival was 7·9 months (6·8-8·9). In 347 (71%) of 488 patients, information regarding treatment-induced xerostomia was available, and 236 (68%) of the 347 patients reported xerostomia after the first cycle of 225 Ac-PSMA RLT. All patients who received more than seven cycles of 225 Ac-PSMA RLT reported xerostomia. Grade 3 or higher anaemia occurred in 64 (13%) of 488 patients, leukopenia in 19 (4%), thrombocytopenia in 32 (7%), and renal toxicity in 22 (5%). No serious adverse events or treatment-related deaths were recorded., Interpretation: 225 Ac-PSMA RLT shows a substantial antitumour effect in mCRPC and represents a viable therapy option in patients treated with previous lines of approved agents. Xerostomia is a common side-effect. Severe bone marrow and renal toxicity are less common adverse events., Funding: None., Competing Interests: Declaration of interests MMS reports grants or contracts from Novartis; payment or honoraria from Bayer, Johnson & Johnson, NTP, and Sanofi; support for attending meetings from the International Atomic Energy Agency; and receipt of equipment or materials from POINT Biopharma. ME reports grants or contracts from Blue Earth Diagnostics; royalties from patent on radiohybrid PSMA; consulting fees from Novartis, Point Biopharma, payment from Novartis; payment for expert testimony from Novartis, Bayer, Telix, and Blue Earth Diagnostics; support for attending meetings from Blue Earth Diagnostics; and patent ownership on radiohybrid PSMA. TH reports grants or contracts from Siemens. CK reports patent ownership. NPL reports contracts from Telix, Ipsen/Ariceum, and Clarity; receipt of educational material from Telix; support for attending meetings from Telix; participation on the advisory board of Telix; and family stock ownership at Clarity. ASi reports support for attending meetings from Telix International, Australia and participation on Data Safety Monitoring Borad for Telix International. RT reports payment or honoraria from Astella, AstraZeneca, Bayer, Bristol Myers Squibb, Janssen, Merck, MSD, Novartis, Orion, Pfizer, Roche, and Sanofi; support for attending meetings from Bayer, Janssen, Orion, Pfizer, and Roche; participation on Data Safety Monitoring Board or Advisory Board of Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Eisei, EUSA, IPSEN, Janssen, Merck, MSD, Novartis, Orion, Pfizer, Philogen, Roche, and Sanofi; stock ownership at Bayer; and financial or non-financial interests at Thieme compliance and Elsevier. AM reports patents owning a patent for treatment of PSMA-expressing cancers. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Metastatic castration-resistant prostate cancer (mCRPC) remains a significant contributor to the global cancer burden. lutetium-177-prostate-specific membrane antigen radioligand therapy ( 177 Lu-PSMA RLT) is an effective salvage treatment. However, studies have highlighted haematologic toxicity as an adverse event of concern. We report our single-centre experience of compassionate access palliative 177 Lu-DOTAGA-(I-y)fk(Sub-KuE) ( 177 Lu-PSMA I&T) with respect to efficacy and haematologic safety., Methods: Patients with mCRPC and adequate bone marrow/liver function were included. All patients included underwent baseline and response assessment by Gallium-68-PSMA-11 positron emission tomography/computed tomography ( 68 Ga-PSMA-11 PET/CT). Prescribed activity of therapy was a median 6.24 GBq per patient per cycle (IQR1.29 GBq), administered in 8-week intervals, up to four cycles. Response was assessed by prostate specific antigen (PSA) and a week-12 PET/CT. Incidence of grade ≥ 3 haematologic toxicity, including association with risk factors (age ≥ 70 years, prior/concurrent therapy, presence of metastases, and number of cycles completed), was analysed., Results: One hundred patients completed one cycle of 177 Lu PSMA I&T and underwent response assessment by both PSA and PET/CT. Two patients had an uninterpretable week-12 PET/CT. Median age was 70 (50-89), median number of prior therapies was three (1-6), and median follow up was 12-months. Fifty-four percent achieved a PSA response. Disease control rate (DCR) by PET/CT was 64% (29% SD, 34% PR, and 1% CR). Disease control by PET/CT was associated with an improved one-year overall survival (OS) compared to non-responders, median OS not-reached vs 10-months ( p < 0.0001; 95% CI: 0.08-0.44). Regarding haematologic toxicity, 11% experienced a grade ≥ 3 cytopenia (self-limiting). No cases of myelodysplasia/acute leukaemia (MDS/AL) have been recorded. No association with risk factors was demonstrated., Conclusion: 177 Lu-PSMA I&T is a safe and effective palliative outpatient treatment for mCRPC. 68 Ga-PSMA-11 PET/CT response is associated with an improved one-year OS and may be used to adapt therapy.

Background: Prostate-specific membrane antigen (PSMA)-based radiopeptide/radioligand therapy represents a rapidly expanding field in the management of metastatic castrate-resistant prostate cancer (mCRPC). However, there remains concern for the development of significant toxicities in heavily pretreated patients. In this study, the authors present their local experience, with respect to efficacy and toxicity, of 22 consecutive patients treated with lutetium-177-DOTAGA-(I-y)fk(Sub-KuE) or 177 Lu-PSMA I&T radioimmunotherapy for progressive mCRPC, followed up over 1 year., Materials and Methods: All patients had progressive mCRPC, an European Cooperative Oncology Group (ECOG) ≤2 with adequate bone marrow and liver function. 177 Lu-PSMA I&T therapy was administered at 8-week intervals with a mean prescribed activity of 5.5 GBq (gigabecquerel) per patient., Results: Twenty patients had evaluable results, median age of 71 years, and median duration of follow-up of 17 months. Three patients (15%) experienced a G1/2 myelotoxicity and four (20%) G3/4. No incidences of myelodysplasia/acute leukemia have been identified. All toxicities were self-limiting. Baseline cytopenia was predictive of the development of subsequent G3/4 myelotoxicity (p = 0.0035). Eight patients (40%) experienced an objective PSA response, with a median time to response of 15 weeks. The median time to PSA progression was not reached. Patients receiving three cycles of therapy were statistically more likely to experience a disease response when compared to those treated with one, two, or four cycles (p < 0.0001)., Conclusions: 177 Lu-PSMA I&T radioimmunotherapy of progressive mCRPC is safe and effective with three cycles being the potential optimal number for determining long-term disease response.

Background: Potentially inappropriate prescriptions (PIPs), associated with adverse drug reactions, hospitalization, and wasteful healthcare spending, are common in elderly patients with comorbidities and multiple drugs., Objective: Our objective was to develop and validate a new tool to reduce PIPs in a hospitalized geriatric population., Methods: This was an observational cohort study of two cohorts (development [n = 100 subjects] and validation [n = 449 subjects]) of consecutive patients aged ≥65 years admitted to geriatric wards from April to December 2012. In the development phase, data on clinical and demographic characteristics, Multidimensional Prognostic Index (MPI), and prescribed drugs before hospital admission were collected and processed using a tool that integrates the Screening Tool of Older Persons' Potentially Inappropriate Prescriptions (STOPP) criteria and the Micromedex™ Drug-Reax System, a drug-management platform. This tool generated a report that was provided to the treating physicians. The weight of the PIPs, as defined by the Medication Appropriateness Index (MAI), was assessed on admission and on discharge. Similar procedures were followed in the validation cohort., Results: PIPs were independently associated with polypharmacy and with prescribing of antithrombotics, sedatives and antidepressants in both cohorts. The use of the tool led to a significant reduction of the MAI score, both in the development (median score 4 [interquartile range; IQR 1-5] vs. 2 [IQR 0-4], p < 0.001) and in the validation cohorts (median 3 [IQR 1-5] vs. 2 [IQR 0-4], p < 0.001)., Conclusion: This tool significantly reduced PIPs, as defined by the MAI score, in a hospitalized geriatric population. This strategy might be useful to minimize inappropriate medication exposure in this group.

The catalytic activity and stereoselectivity of complexes [Pd(eta(1),eta(2)-C(8)H(12)OMe)(Ar--N==C(R')--C(R')==N--Ar)]X in the copolymerization of CO and p-methylstyrene have been correlated with their interionic structure in solution and in the solid state, as determined by (19)F,(1)H-HOESY NMR spectroscopy and X-ray diffraction studies, respectively. The highest productivity is obtained with unhindered diimine ligands bearing electron-donating substituents and with the least coordinating counterion. Copolymers with a microstructure ranging from atactic to predominantly isotactic are obtained. The degree of isotacticity increases as the steric hindrance in the apical positions and the coordinating ability of the counterion increase. The counterion is located close to the diimine in both solution and the solid state but it moves toward the palladium as the steric hindrance in the apical positions decreases. When the latter is small the counterion competes with the substrate for apical coordination, and consequently it affects the productivity. In the case of ortho-dimethyl-substituted ligands the counterion is confined in the back, above the N==C(R')--C(R')==N moiety, and does not affect the productivity. However, it contributes to increasing the stereoregularity of the copolymer by making the aryl moieties more rigid. With R'=Me and Ar=o-Me(2)C(6)H(3) an ll of 81 % and 72 % was obtained with X(-)=CF(3)SO(3) (-) or BArF(-), respectively. The isotacticity of the copolymers produced by ortho-monosubstituted catalysts depends greatly on the counterion and ranges from 30 % to 59 % with X(-)=BArF(-) and X(-)=CF(3)SO(3) (-), respectively, with Ar=o-EtC(6)H(4) and R'=Me. Based on the interionic structural results, this effect can be explained by a greater reduction of the copolymerization rate of C(s)-symmetric isomers with respect to their C(2)-symmetric counterparts.

The aggregation tendency of complexes [Ru(eta6-cymene)(N,O)Cl]X [N,O = 2-benzoylpyridine (2-bzpy), 1, and 2-acetylpyridine (2-acpy), 2, X- = BPh4- or PF6-] has been studied by means of PGSE NMR experiments. It was found that complexes with PF6- as counterion are mainly present in CD2Cl2 as ion pairs at low concentration, as a mixture of ion triples and free anions at medium concentration and as ion quadruples at elevated concentration. 19F, 1H-HOESY NMR experiments revealed that in ion triples and ion quadruples two cationic Ru-units pair up. Consistently, in the solid-state structure of 1PF6, determined through X-ray single-crystal investigation, two cationic Ru-units are held together by an intermolecular pi-pi stacking interaction between the pyridyl rings. Complexes having BPh4- as counterion are only present in solution as even aggregates, namely ion pairs at low concentration and ion quadruples at elevated concentration. In such a case a counteranion bridges two cationic Ru-units as observed in the solid-state structure of 1BPh4. The reactivity of complexes 1-2 toward AgX salts has been investigated in different solvents. Bicationic [Ru(eta6-cymene)(N,O)(MeCN)]X2 (N,O = 2-bzpy, 3, and 2-acpy, 4) and [Ru(MeCN)4(N,O)]X2 (N,O = 2-bzpy, 5, and 2-acpy, 6) complexes were obtained by the reaction of 1 and 2 with AgX in the presence of three equivalents of acetonitrile or in acetonitrile, respectively. The reaction of 1 with AgPF6 in acetone afforded complex [Ru(eta6-cymene)(N,O,O)]PF6 (7, where N,O,O = 4-alcoxide-4-phenyl-4-(pyridin-2-yl)butan-2-one) from the C-C coupling of a deprotonated methyl group of the coordinated acetone and the C=O moiety of 2-bzpy ligand.

Purpose: Selective internal radiation therapy (SIRT) with SIR-Spheres(R) is a new technique for selectively targeting high doses of radiation to tumours within the liver. The primary objectives of this randomised trial were to compare the response rate, time to progressive disease (PD), and toxicity of a regimen of systemic fluorouracil/leucovorin chemotherapy versus the same chemotherapy plus a single administration of SIR-Spheres in patients with advanced colorectal liver metastases. The trial was designed to presage a larger trial that would have survival as the primary outcome., Patients and Methods: Twenty-one patients with previously untreated advanced colorectal liver metastases, with or without extrahepatic metastases, were randomised into the study., Results: Using RECIST criteria, the response rate for 11 patients receiving the combination treatment was significantly greater than for 10 patients receiving chemotherapy alone (First Integrated Response; 10 PR, 1 SD vs. 0 PR, 6 SD, 4 PD, P < 0.001 and Best Confirmed Response; 8 PR, 3 SD vs. 0 PR, 6 SD, 4 PD P < 0.001). The time to PD was greater for patients receiving the combination treatment (18.6 months vs. 3.6 months, P < 0.0005). Median survival was significantly longer for patients receiving the combination treatment (29.4 months vs. 12.8 months, P = 0.02). One patient in the combination arm died from chemotherapy induced neutropenic sepsis after the fourth chemotherapy cycle. There were more Grade 3 and 4 toxicity events in patients receiving the combination treatment. There was no difference in quality-of-life over a 3 month period between the two treatments when rated by patients (P = 0.96) or physicians (P = 0.98)., Conclusions: This small phase 2 randomised trial demonstrated that the addition of a single administration of SIR-Spheres to a regimen of systemic fluorouracil/leucovorin chemotherapy significantly increased both treatment related response, time to PD, and survival with acceptable toxicity. The combination of SIR-Spheres plus systemic chemotherapy is now the subject of ongoing trials to further define patient benefit., ((c) 2004 Wiley-Liss, Inc.)

PGSE and NOE NMR measurements were carried out for complexes [Ru(eta(6)-cymene)((2-R-C(6)H(4))N=C(Me)-C(Me)=N(2-R-C(6)H(4)))Cl]X (X = BF(4) or BPh(4)) in both protic and aprotic solvents with a relative permettivity (epsilon(r)) ranging from 2.27 (benzene-d(6)) to 46.45 (dimethyl sulfoxide-d(6)). PGSE and NOE results indicate that complexes have a tendency to aggregate even in medium-polarity solvents such as ethanol (epsilon(r) = 24.55) and methanol (epsilon(r) = 32.66). In addition, the aggregation process is favored by a decrease of epsilon(r) and, unexpectedly, by protic solvents. NOE measurement investigations, interpreted with the help of theoretical calculations and confirmed by X-ray single crystal studies, suggest different aggregation processes for the two counteranions: two cationic moieties approach each other when X = BF(4) while the anion bridges two cationic moieties when X = BPh(4).

The structure of the Ru(II) ion pairs trans-[Ru(COMe)[(pz(2))CH(2)](CO)(PMe(3))(2)]X (X(-) = BPh(4)(-), 1a; BPh(3)Me(-), 1b; BPh(3)(n-Bu)(-), 1c; BPh(3)(n-Hex)(-), 1d; B(3, 5-(CF(3))(2)(C(6)H(3)))(4)(-), 1e; PF(6)(-), 1f; and BF(4)(-), 1g; pz = pyrazol-1-yl-ring) was investigated in solution from both a qualitative (chloroform-d, methylene chloride-d(2), nithromethane-d(3)) and quantitative (methylene chloride-d(2)) point of view by performing 1D- and 2D-NOE NMR experiments. In particular, the relative anion-cation localization (interionic structure) was qualitatively determined by (1)H-NOESY and (19)F, (1)H-HOESY (heteronuclear Overhauser effect spectroscopy) NMR experiments. The counteranion locates close to the peripheral protons of the bispyrazolyl ligand independent of its nature and that of the solvent. In complexes 1c and 1d bearing unsymmetrical counteranions, the aliphatic chain points away from the metal center as indicated by the absence of NOE between the terminal Me group and any cationic protons. An estimation of the average interionic distances in solution was obtained by the quantification of the NOE build-up versus the mixing time under the assumption that the interionic and intramolecular correlation times (tau(c)) are the same. Such an assumption was checked by the experimental measurements of tau(c) from both the dipolar contribution to the carbon-13 longitudinal relaxation time T(DD-1)and the comparison of the intramolecular and interionic cross relaxation rate constant (sigma) dependence on the temperature. Both the methodologies indicate that anion and cation have comparable tau(c) values. The determined correlation time values were compared with those obtained for the neutral trans-[Ru(COMe)[(pz(2))BH(2)](CO)(PMe(3))(2)] complex (2), isosteric with the cation of 1. They were significantly shorter (approximately 3.8 times), indicating that the main contribution to dipolar relaxation processes comes from the overall ion pair rotation. As a consequence, the determined average interionic distances appear to be accurate. By using such interionic distances, it was possible to verify that the counteranion in complex 1b also orients the BMe group far away from the metal center.

Unlabelled: Interpretation of radionuclide arthrograms (RNA) of the knee after total knee joint replacement (TKR) may be difficult because of the lack of sufficient anatomic reference information. Additional transmission images may provide the necessary reference information required for correct interpretation of RNA of the knee., Methods: Tc-99m tin colloid (20 MBq) RNA was combined with cobalt-57 transmission imaging in six patients with painful TKRs in whom loosening of the TKR was suspected. Knee surgery was then performed on these six cases., Results: RNA correctly detected loosening of the tibial component in five of six cases, but did not detect loosening of the femoral component in any of three cases., Conclusion: RNA combined with transmission imaging is recommended for detection of loosening of the tibial component of a TKR. RNA may not be of value for detecting loosening of the femoral component.

Amoxicillin when administered with gastric acid suppressors has been shown to be effective in eradication of Helicobacter pylori in 50 to 80% of subjects. The aim of this investigator-blind crossover study was to determine if gastric mucosal amoxicillin uptake was affected by increasing gastric juice pH. Fifteen male subjects (7 H. pylori positive and 8 H. pylori negative) were randomized to receive 150 mg of ranitidine twice a day, 300 mg of ranitidine twice a day, or no drug for 2 days prior to upper endoscopy. The last dose of ranitidine was given 60 min prior to upper endoscopy, and amoxicillin (500 mg) was given 30 min prior to upper endoscopy. The amoxicillin concentrations in mucosal biopsy samples, gastric juice, and serum were determined by a standard microbiological bioassay technique. Mean amoxicillin levels were greater in samples of antrum, fundus, and duodenum for volunteers who received no ranitidine than in those receiving 300 mg of ranitidine (P < 0.05) and those receiving 150 mg of ranitidine (P < 0.05 except for fundus). Amoxicillin levels in the antrum, fundus, and duodenum were negatively correlated with gastric juice pH (P < 0.005 for antrum; P < 0.001 for fundus and duodenum). There was no correlation between gastric juice pH and amoxicillin levels in either gastric juice or serum. The amoxicillin concentration in gastric juice was significantly higher with 300 mg of ranitidine than with no ranitidine (P < 0.05). Thus, lower gastric juice pH is associated with a higher rate of mucosal uptake of amoxicillin.

Chronic immune thrombocytopaenia is an immunologically mediated disorder resulting in disordered platelet kinetics and potentially life-threatening thrombocytopaenia. Failure of medical therapy is an indication for splenectomy, and responses are seen in 80% of patients following this procedure. An important cause of relapse following splenectomy is the presence of an accessory spleen. We describe a patient with Hodgkin's Disease who developed chronic immune thrombocytopaenia despite previous splenectomy. A remission was induced with immunosuppressive therapy, but he later relapsed. An accessory spleen was detected using 99mTc denatured red blood cells and localized using computed tomography (CT). Resection of the accessory spleen resulted in clinical remission. Accessory spleens are often small in size. Combined modality imaging is recommended in the evaluation of patients with a possible accessory spleen.

Heterotopic calcification occurs commonly in spinal cord injured patients and following joint trauma or surgery. 99Tcm-methylene diphosphonate is useful in the detection of these lesions, many of which are subclinical. Three patients are presented with heterotopic calcification, one with severe hypoxic encephalopathy and two following major trauma. Intense 67Ga uptake within areas of heterotopic calcification was noted in all three patients. Two of the patients also underwent 99Tcm-methylene diphosphonate bone scanning and showed uptake of the bone agent corresponding to the areas of 67Ga uptake. In predisposed patients, heterotopic calcification should be considered in the differential diagnosis of a focal area of 67Ga uptake.