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Preliminary studies on a radioactive antibody against the neural cell adhesion molecule (NCAM) demonstrated a significant accumulation of [ 131 I]I-ERIC1 in neuroblastoma tumor cells in mice. This study aims to validate the therapeutic efficacy and potential adverse effects of these radioactive immunoconjugates (RICs) in neuroblastoma-bearing mice. To determine the highest tolerated dose, healthy SCID mice received 1 to 22 MBq of [ 131 I]I-ERIC1, with the survival time measured. Tumor response was evaluated by administering 0.8 to 22 MBq of [ 131 I]I-ERIC1 to neuroblastoma-bearing mice and assessing tumor size and systemic toxicity through body weight, blood counts, and survival. It was observed that doses up to approximately 3 MBq per animal (150 MBq/kg) were well tolerated, whereas higher doses resulted in systemic toxicity and death. The neuroblastomas exhibited a dose-dependent response, with optimal therapeutic efficacy achieved at 1.8-2.5 MBq per animal (90-125 MBq/kg), significantly extending survival by a factor of five. The antibody ERIC1 is a promising vehicle for the transport of beta emitters into NCAM-positive tumor tissue. An optimal dosage of the [ 131 I]I-ERIC1 antibody can be established with a balance of tumor-static effects and adverse effects, resulting in a marked extension of survival time.

This study evaluates the efficacy of [ 131 I]I-ERIC1 in targeting and inhibiting the growth of SCLC tumors in mice, focusing on tumor accumulation and regression and potential side effects. NCAM-positive NCI-H69 SCLC cells were implanted in CB 17 SCID mice, and [ 131 I]I-ERIC1 biokinetics were measured in organs and tissues at four post-injection time points (24, 72, 96, and 120 h). The experimental series compared tumor growth, survival, and changes in blood counts among three treatment groups (1, 2, or 3 MBq) and a control group, with treatments initiated either two or five days post implantation. [ 131 I]I-ERIC1 was synthesized with >95% radiochemical purity and a specific activity of 15 TBq/mmol. Tumor activity peaked at 31.5 ± 6.6% ID/g after four days, demonstrating significant antitumor efficacy, which resulted in sustained remission and extended survival. Hematological toxicity was observed, with the optimal dose identified as 2 MBq per animal administered two days post implantation. [ 131 I]I-ERIC1 shows promise as a theranostic agent for personalized cancer treatment by effectively targeting SCLC tumors with manageable side effects. However, further studies are required to optimize dosing strategies and minimize toxicity., Competing Interests: The authors declare no conflict of interest.

The preparation of 24 estrogens, their estrogen receptor (ER) affinity and studies of radioiodinated estrogen binding to ER-positive male bladder tumor cells (HTB9) are described. The estrogens with the highest affinity were selected using fluorescence anisotropy assays. A 2,2,2-trifluoroethyl group at the 11β-position caused particularly promising affinity. (Radio)iodination was performed on the 17α-vinyl group. Binding studies on HTB9 cells revealed picomolar affinities of radioconjugates 19 and 31, indicating promising ability for targeting of urogenital tumors.

Purpose: We present here a Zr-89-labeled inhibitor of prostate-specific membrane antigen (PSMA) as a complement to the already established F-18- or Ga-68-ligands., Procedures: The precursor PSMA-DFO (ABX) was used for Zr-89-labeling. This is not an antibody, but a peptide analogue of the precursor for the production of [ 177 Lu]Lu-PSMA-617. The ligand [ 89 Zr]Zr-PSMA-DFO was compared with [ 68 Ga]Ga-PSMA-11 and [ 18 F]F-JK-PSMA-7 in vitro by determination of the K d value, cellular uptake, internalization in LNCaP cells, biodistribution studies with LNCaP prostate tumor xenografts in mice, and in vivo by small-animal PET imaging in LNCaP tumor mouse models. A first-in-human PET was performed with [ 89 Zr]Zr-PSMA-DFO on a patient presenting with a biochemical recurrence after brachytherapy and an ambiguous intraprostatic finding with [ 18 F]F-JK-PSMA-7 but histologically benign cells in a prostate biopsy 7 months previously., Results: [ 89 Zr]Zr-PSMA-DFO was prepared with a radiochemical purity ≥ 99.9% and a very high in vitro stability for up to 7 days at 37 °C. All radiotracers showed similar specific cellular binding and internalization, in vitro and comparable tumor uptake in biodistribution experiments during the first 5 h. The [ 89 Zr]Zr-PSMA-DFO achieved significantly higher tumor/background ratios in LNCaP tumor xenografts (tumor/blood: 309 ± 89, tumor/muscle: 450 ± 38) after 24 h than [ 68 Ga]Ga-PSMA-11 (tumor/blood: 112 ± 57, tumor/muscle: 58 ± 36) or [ 18 F]F-JK-PSMA-7 (tumor/blood: 175 ± 30, tumor/muscle: 114 ± 14) after 4 h (p < 0.01). Small-animal PET imaging demonstrated in vivo that tumor visualization with [ 89 Zr]Zr-PSMA-DFO is comparable to [ 68 Ga]Ga-PSMA-11 or [ 18 F]F-JK-PSMA-7 at early time points (1 h p.i.) and that PET scans up to 48 h p.i. clearly visualized the tumor at late time points. A late [ 89 Zr]Zr-PSMA-DFO PET scan on a patient with biochemical recurrence (BCR) had demonstrated intensive tracer accumulation in the right (SUV max 13.25, 48 h p.i.) and in the left prostate lobe (SUV max 9.47), a repeat biopsy revealed cancer cells on both sides., Conclusion: [ 89 Zr]Zr-PSMA-DFO is a promising PSMA PET tracer for detection of tumor areas with lower PSMA expression and thus warrants further clinical evaluation., (© 2021. The Author(s).)

In this article we summarize suspected adverse events following immunization (AEFI) of pericarditis, myocarditis and perimyocarditis that were reported by our regional pharmacovigilance centre after COVID-19 mRNA-vaccination and discuss their association with these vaccines. Seventeen cases were reported between March and July 2021. Of these, nine had perimyocarditis, five myocarditis and three pericarditis. Twelve patients were male (71%). The median age was 38 years (range 17-88). The most commonly observed presenting symptom was acute chest pain (65%). While 47% of the patients were previously healthy, 53% had at least one pre-existing comorbidity, with hypertension being the most prevalent (24%). The European Society of Cardiology diagnostic criteria for the reported AEFIs were fulfilled in twelve cases (71%). The AEFIs occurred after the first vaccine dose in six cases (35%), after the second vaccine dose in ten cases (59%) and after both doses in one case (6%). The median latency of all AEFIs taken together was 14 days (range 1-28) after the first vaccination and 3 days (range 1-17) after the second one. All patients except one were hospitalized (94%) with a median length of stay of 7.5 days (range 3-13). The majority of patients ( n  = 11, 65%) did not experience any complications, and 13 (77%) of the patients had recovered or were recovering at the time of discharge. In 16 of the 17 cases (94%), the association between the AEFI and mRNA-vaccination was considered possible by the pharmacovigilance centre., (Copyright ©2021 The Author(s).)

In this article we summarize the cardiovascular adverse events that were observed in three patients during their treatment for COVID-19 and discuss their association with lopinavir/ ritonavir (LPV/r) and hydroxychloroquine (HCQ). The cases were reported to our regional pharmacovigilance centre in April 2020. All three patients were above 75 years in age, male and multimorbid, and had been hospitalized for treatment of COVID-19. As part of their treatment, all of them received a very strictly monitored off-label therapy with LPV/r and HCQ, for which they had given their prior, written, informed consent. In one patient, erythromycin was also administered. All three patients developed a significant QTc time prolongation during or shortly after therapy with the above drugs. On account of this, the treatment had to be discontinued early in each case and QTc time recovered in all three patients., (Copyright ©2021 The Author(s).)

Background: With the increasing utilization of (68)Ge-(68)Ga radionuclide generators, (68)Ga labelled peptides like DOTATATE are receiving more attention in nuclear medicine. On the one hand, the long half-life of the parent nuclide (68)Ge is an enormous advantage for routine applications, but the question of the long-term stability of the (68)Ge breakthrough arises, which up to now has scarcely been investigated., Method: A sum of 123 eluates from four different (68)Ge-(68)Ga generators (iThemba Labs, Faure, South Africa) and 115 samples of the prepared radiopharmaceutical (68)Ga-DOTATATE were measured first with a dose calibrator and again after decay of the eluted (68)Ga via gamma-ray spectrometry. A complete decay curve was recorded for one sample eluate. A further three eluates were eluted in ten fractions of 0.5 ml in order to obtain detailed information concerning the distribution of the two nuclides within the eluates. The influences of factors such as the amount of DOTATATE, addition of Fe(3+) salts and replacement of HEPES buffer with sodium acetate on the radiochemical synthesis were also tested., Results: The content of long-lived (68)Ge breakthrough increases over the entire period of use to more than 100 ppm. The labelling process with the chelator DOTA removes (68)Ge efficiently. The maximum activity found in the residues of the radiopharmaceuticals investigated in this study was below 10 Bq in nearly all cases. In many cases (12% of the labelled substance), the long-lived parent nuclide could not be identified at all. The labelling process is still viable for reduced amounts of the chelator and with acetate buffer., Conclusion: Effective doses received by the patient from (68)Ge in the injected radiopharmaceutical (68)Ga-DOTATATE are lower than 0.1 μSv and are therefore practically negligible, especially when compared with the contribution of the PET radiopharmaceutical itself. Gamma-ray spectrometry as recommended by the European Pharmacopeia is suitable for quantification of radionuclidic impurities.

Aim: This in-vitro study investigated the influence of the contrast agents iothalamate (Conray) and special preparations of iotrolan (Isovist) and iopromide (Ultravist) without ethylenediaminetetraacetic acid (EDTA), the anaesthetic Scandicain and the glucocorticoid triamcinolone on the stability of 90Y-, 169Er- and 186Re-radiocolloids used for radiation synovectomy., Methods: Vials of 1 ml of synovial fluid and 0.02 ml of radiocolloid suspension (0.56-3.6 MBq) were mixed with 0.06, 0.6 and 1.0 ml of each contrast agent. In an additional series, 0.1 ml of Scandicain and 0.1 ml of triamcinolone were tested. Thin layer chromatography and ultrafiltration/centrifugation were performed between 1 h and 15 days after incubation with negative and positive controls., Results: Within 24 h, 0.6 and 1.0 ml of Conray had mobilized 5-20% of the 90Y and 169Er out of the colloids. No interference between 186Re-colloids and Conray was visible before the ninth day after incubation. Iotrolan and iopromide without EDTA had no effect on the stability at shorter incubation periods of up to 6 days. The addition of Scandicain did not produce low-molecular 90Y or 169Er in the presence of synovial fluid. The fraction of low-molecular 186Re reached 4% after 24 h. Triamcinolone did not have any effect on stability in the presence of synovial fluid., Conclusion: The disintegration of the radioactive colloids can be attributed to either the formation of EDTA complexes or radiolytic effects. The volume of the injected contrast agent should be as small as possible to confirm correct intra-articular distribution.