Low-dose CT from myocardial perfusion SPECT/CT allows the detection of anemia in preoperative patients

BACKGROUND To assess whether low-dose CT for attenuation correction of myocardial perfusion single-photon emission computed tomography (SPECT) allows for identification of anemic patients and grading anemia severity. METHODS AND RESULTS Patients who underwent a preoperative blood-test and low-dose CT scan, as a part of a cardiac SPECT exam, between 01 January 2015 and 31 December 2017 were enrolled in this retrospective study. Hemoglobin (Hb) levels and hematocrit were derived from clinical records. CT images were visually assessed (qualitative analysis) for the detection of inter-ventricular septum sign (IVSS) and aortic rim sign (ARS) and quantitative analysis were performed. The diagnostic accuracy for detecting anemia was compared using Hb values as the standard of reference. A total of 229 patients were included (110 with anemia; 57 mild; 46 moderate; 7 severe). The AUC of IVSS and ARS were 0.830 and 0.669, respectively (p<0.0001). The quantitative analysis outperformed ARS and IVSS; (AUC of 0.893, p=0.29). The optimal anemia cut-off using Youden index was 4.5 HU. CONCLUSION Quantitative analysis derived from low-dose CT images, as a part of cardiac SPECT exams, have a diagnostic accuracy similar to that of hematocrit for the detection of anemia and may allow discriminating different anemia severities

Phase I clinical study of the recombinant antibody toxin scFv(FRP5)-ETA specific for the ErbB2/HER2 receptor in patients with advanced solid malignomas

INTRODUCTION: ScFv(FRP5)-ETA is a recombinant antibody toxin with binding specificity for ErbB2 (HER2). It consists of an N-terminal single-chain antibody fragment (scFv), genetically linked to truncated Pseudomonas exotoxin A (ETA). Potent antitumoral activity of scFv(FRP5)-ETA against ErbB2-overexpressing tumor cells was previously demonstrated in vitro and in animal models. Here we report the first systemic application of scFv(FRP5)-ETA in human cancer patients. METHODS: We have performed a phase I dose-finding study, with the objective to assess the maximum tolerated dose and the dose-limiting toxicity of intravenously injected scFv(FRP5)-ETA. Eighteen patients suffering from ErbB2-expressing metastatic breast cancers, prostate cancers, head and neck cancer, non small cell lung cancer, or transitional cell carcinoma were treated. Dose levels of 2, 4, 10, 12.5, and 20 μg/kg scFv(FRP5)-ETA were administered as five daily infusions each for two consecutive weeks. RESULTS: No hematologic, renal, and/or cardiovascular toxicities were noted in any of the patients treated. However, transient elevation of liver enzymes was observed, and considered dose limiting, in one of six patients at the maximum tolerated dose of 12.5 μg/kg, and in two of three patients at 20 μg/kg. Fifteen minutes after injection, peak concentrations of more than 100 ng/ml scFv(FRP5)-ETA were obtained at a dose of 10 μg/kg, indicating that predicted therapeutic levels of the recombinant protein can be applied without inducing toxic side effects. Induction of antibodies against scFv(FRP5)-ETA was observed 8 days after initiation of therapy in 13 patients investigated, but only in five of these patients could neutralizing activity be detected. Two patients showed stable disease and in three patients clinical signs of activity in terms of signs and symptoms were observed (all treated at doses ≥ 10 μg/kg). Disease progression occurred in 11 of the patients. CONCLUSION: Our results demonstrate that systemic therapy with scFv(FRP5)-ETA can be safely administered up to a maximum tolerated dose of 12.5 μg/kg in patients with ErbB2-expressing tumors, justifying further clinical development

Induction of effective and antigen-specific antitumour immunity by a liposomal ErbB2/HER2 peptide-based vaccination construct

Efficient delivery of tumour-associated antigens to appropriate cellular compartments of antigen-presenting cells is of prime importance for the induction of potent, cell-mediated antitumour immune responses. We have designed novel multivalent liposomal constructs that co-deliver the p63–71 cytotoxic T Lymphocyte epitope derived from human ErbB2 (HER2), and HA307–319, a T-helper (Th) epitope derived from influenza haemagglutinin. Both peptides were conjugated to the surface of liposomes via a Pam3CSS anchor, a synthetic lipopeptide with potent adjuvant activity. In a murine model system, vaccination with these constructs completely protected BALB/c mice from subsequent s.c. challenge with ErbB2-expressing, but not ErbB2-negative, murine renal carcinoma (Renca) cells, indicating the induction of potent, antigen-specific immune responses. I.v. re-challenge of tumour-free animals 2 months after the first tumour cell inoculation did not result in the formation of lung tumour nodules, suggesting that long-lasting, systemic immunity had been induced. While still protecting the majority of vaccinated mice, a liposomal construct lacking the Th epitope was less effective than the diepitope construct, also correlating with a lower number of CD8+ IFN-γ+ T-cells identified upon ex vivo peptide restimulation of splenocytes from vaccinated animals. Importantly, in a therapeutic setting treatment with the liposomal vaccines resulted in cures in the majority of tumour-bearing mice and delayed tumour growth in the remaining ones. Our results demonstrate that liposomal constructs which combine Tc and Th peptide antigens and lipopeptide adjuvants can induce efficient, antigen-specific antitumour immunity, and represent promising synthetic delivery systems for the design of specific antitumour vaccines

Low-dose CT from myocardial perfusion SPECT/CT allows the detection of anemia in preoperative patients

BACKGROUND: To assess whether low-dose CT for attenuation correction of myocardial perfusion single-photon emission computed tomography (SPECT) allows for identification of anemic patients and grading anemia severity. METHODS AND RESULTS: Patients who underwent a preoperative blood-test and low-dose CT scan, as a part of a cardiac SPECT exam, between 01 January 2015 and 31 December 2017 were enrolled in this retrospective study. Hemoglobin (Hb) levels and hematocrit were derived from clinical records. CT images were visually assessed (qualitative analysis) for the detection of inter-ventricular septum sign (IVSS) and aortic rim sign (ARS) and quantitative analysis were performed. The diagnostic accuracy for detecting anemia was compared using Hb values as the standard of reference. A total of 229 patients were included (110 with anemia; 57 mild; 46 moderate; 7 severe). The AUC of IVSS and ARS were 0.830 and 0.669, respectively (p<0.0001). The quantitative analysis outperformed ARS and IVSS; (AUC of 0.893, p=0.29). The optimal anemia cut-off using Youden index was 4.5 HU. CONCLUSION: Quantitative analysis derived from low-dose CT images, as a part of cardiac SPECT exams, have a diagnostic accuracy similar to that of hematocrit for the detection of anemia and may allow discriminating different anemia severities. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12350-021-02899-x