Excel Diagnostics Imaging

Abstract BACKGROUND Low-density lipoprotein receptors (LDLR) are overexpressed in a variety of solid tumors, including glioblastoma (GBM), and are known to play a key role in tumor proliferation and metabolic regulation.-LDLRs are also expressed on the blood-brain barrier (BBB), offering a unique gateway for receptor-mediated delivery of radiopharmaceuticals to intracranial tumors. In this study, we present initial data from eIND on the use of a novel LDLR-targeted imaging agent, ⁶⁸Ga-RMX-VH, in patients with newly diagnosed or recurrent GBM, We will also discuss the selection of the second-generation RMX_VH_PKM, which features modified blood circulation times and improved tumor-targeting properties. METHODS We initiated an open-label, single-dose, eIND-study (#155880) using 68Ga-RMX-VH PET/CT in newly diagnosed or recurrent patients with GBM. The primary objective was to assess the biodistribution and dosimetry of 68Ga-RMX-VH. The secondary objective was to correlate the extent of GBM visualized by contrast-enhanced MRI of the brain with the distribution of 68Ga-RMX-VH PET/CT in the brain, in each subject. A total of 10 GBM subjects have been scheduled for enrollment, with 5 of them enrolled in the dosimetry group. RESULTS We enrolled four patients with glioblastoma (GBM) (3 males, 1 female, aged 58–68 years) who had undergone craniotomy, adjuvant chemotherapy, and/or radiation therapy (XRT) and exhibited disease progression on MRI/CT scans. Pathological evaluation confirmed GBM with MGMT promoter methylation, IDH wild-type status, and EGFR mutation (Ki-67 = 25–60%). PET/CT imaging with ⁶⁸Ga-RMX-VH demonstrated effective targeting of the solid portion of the residual tumor, correlating well with contrast-enhanced regions on MRI or FLAIR. Activity was primarily cleared via the kidneys. These results stimulated our work on the selection of the second-generation RMX-VH-PKM, which has a longer blood circulation time and improved tumor–specific retention, as confirmed in vivo studies. CONCLUSIONS RMX-VH agents effectively target LDLR-overexpressing glioblastoma (GBM), with ⁶⁸Ga- or 203Pb-labeled radiotracer uptake closely aligning with enhanced and FLAIR regions on brain MRI.

Yttrium-90 FF-21101 (90Y-FF-21101) is a radiopharmaceutical that targets P-cadherin as a therapy against solid tumors. A previously reported, first-in-human study determined that a dose of 25 mCi/m2 was safe, and a patient with clear cell carcinoma of the ovary achieved a complete response. In this article, the authors report the results of 90Y-FF-21101 treatment in an ovarian carcinoma expansion cohort and in patients with selected solid tumors who had known high P-cadherin expression. The trial was conducted as an open-label study in patients with advanced/metastatic disease. Radiologic response and safety were evaluated in patients who received 25 mCi/m2 intravenously once every three cycles of 28 days until they developed progressive disease. Evaluation of the ovarian cohort was conducted in a Simon two-stage manner to determine further enrollment. Fifty-seven patients (20 with ovarian carcinoma) were enrolled and treated. Patients who had ovarian and solid tumors had received a median of five and three prior therapies, respectively. No complete or partial responses were observed, so the trial was ended. The median progression-free survival was 118 days for the ovarian cohort and 55 days for the solid-tumor cohort. The most common treatment-related adverse events were thrombocytopenia (40%) and neutropenia (54%). One patient each developed fatal veno-occlusive disease and intracranial hemorrhage. Patients with higher P-cadherin levels remained on the study longer. 90Y-FF-21101 did not meet the predefined efficacy criteria, and adverse events were consistent with 90Y agents. These data may assist in the development of other P-cadherin-directed therapies (ClinicalTrials.gov identifier NCT02454010).

O presente trabalho discute os protocolos de consulta como manifestação da autodeterminação dos povos indígenas sob a ótica do pluralismo jurídico. Analisa o direito de consulta previsto no texto da Convenção 169 da OIT, ratificada no Brasil na esteira da derrocada do pensamento integracionista. Discute os protocolos de consulta, ou seja, normas consuetudinárias dos povos indígenas, produzidas descentralizadamente com a finalidade de regular os procedimentos a serem seguidos na consulta, para que ela seja culturalmente adequada. Discute o liame existente entre as correntes de pluralismo jurídico e a proteção dos direitos coletivos dos povos indígenas, no contexto do ganho de legitimidade da justiça comunitária e consuetudinária, voltada às necessidades dos povos. O trabalho baseia-se na pesquisa exploratória bibliográfica e documental, utilizando o método de abordagem analítico como base para a reflexão crítica sobre os protocolos. Constata que os protocolos surgem a partir de um contexto de lutas, na busca da efetivação dos direitos positivados na Constituição e na Convenção 169 OIT. Constata que se a consulta não estiver em consonância com os protocolos, fica descaracterizada, esvaziando-se o princípio da autodeterminação. Conclui-se que os movimentos pluralistas conferem legitimidade para os protocolos de consulta, os quais são expressões por excelência do pluralismo jurídico.

PurposePostoperative infection still constitutes an important complication of spine surgery, and the optimal imaging modality for diagnosing postoperative spine infection has not yet been established. The aim of this prospective multicenter study was to assess the diagnostic performance of three imaging modalities in patients with suspected postoperative spine infection: MRI, [18F]FDG PET/CT, and SPECT/CT with 99mTc-UBI 29-41.MethodsPatients had to undergo at least 2 out of the 3 imaging modalities investigated. Sixty-three patients enrolled fulfilled such criteria and were included in the final analysis: 15 patients underwent all 3 imaging modalities, while 48 patients underwent at least 2 imaging modalities (MRI + PET/CT, MRI + SPECT/CT, or PET/CT + SPECT/CT). Final diagnosis of postoperative spinal infection was based either on biopsy or on follow-up for at least 6 months. The MRI, PET/CT, and SPECT/CT scans were read blindly by experts at designated core laboratories. Spine surgery included metallic implants in 46/63 patients (73%); postoperative spine infection was diagnosed in 30/63 patients (48%).ResultsSignificant discriminants between infection and no infection included fever (P = 0.041), discharge at the wound site (P < 0.0001), and elevated CRP (P = 0.042). There was no difference in the frequency of infection between patients who underwent surgery involving spinal implants versus those who did not. The diagnostic performances of MRI and [18F]FDG PET/CT analyzed as independent groups were equivalent, with values of the area under the ROC curve equal to 0.78 (95% CI: 0.64–0.92) and 0.80 (95% CI: 0.64–0.98), respectively. SPECT/CT with 99mTc-UBI 29-41 yielded either unacceptably low sensitivity (44%) or unacceptably low specificity (41%) when adopting more or less stringent interpretation criteria. The best diagnostic performance was observed when combining the results of MRI with those of [18F]FDG PET/CT, with an area under the ROC curve equal to 0.938 (95% CI: 0.80–1.00).Conclusion[18F]FDG PET/CT and MRI both possess equally satisfactory diagnostic performance in patients with suspected postoperative spine infection, the best diagnostic performance being obtained by combining MRI with [18F]FDG PET/CT. The diagnostic performance of SPECT/CT with 99mTc-UBI 29-41 was suboptimal in the postoperative clinical setting explored with the present study.

Abstract Introduction: Peptide Receptor Radioligand Therapy (PRRT) has been shown to be an effective treatment for patients with metastatic somatostatin receptor (SSTR) positive neuroendocrine tumors (NETs), however interest in developing alpha-emitter based therapies remains high. We present the initial safety and preliminary efficacy of this first-in-human (FIH) study of AlphaMedix™ (212Pb-DOTAMTATE), a novel somatostatin analog for Targeted Alpha-emitter Therapy (TAT), in patients with SSTR expressing NETs (FDA IND 135150). Methods: Thirteen adult subjects, 6 men and 7 women, median age 68 (range 27-75), with biopsy-proven unresectable or metastatic SSTR (+) NETs from different primary sites (small bowel, pancreas, and lung) with at least one measurable lesion were treated with a Single, weight-based, Ascending Dose (SAD) of AlphaMedix™. Dose escalation was conducted according to a classic 3+3 design. Once a partial response was observed in the SAD-3 cohort, the Multiple Ascending Dosing (MAD) began at the same dose level (3 cycles dosed every 8-weeks). Subjects who had previously received PRRT were excluded. All patients received amino acid renal protection prior to AlphaMedixTM administration. Response to treatment was measured per RECIST 1.1 and the effect on the quality of life was measured with the EORTC-QLQ-C30 QOL questionnaire. Two SAD cohorts (SAD1 and SAD2) received 30.7 and 40.0 µCi/kg respectively. MAD3 received 52.0 µCi/kg per cycle and MAD4, began dosing at 67.6 µCi/ kg for a total dose ranging from 14.7 to 16.8 mCi, across 3 cycles. Results: All 3 subjects in MAD 4 who received 67.6 µCi/ kg for 3 cycles showed partial response with 73%, 71%, and 33% decrease in size of the index lesions respectively. 68Ga DOTATATE PET/CT revealed almost a complete response in 2 subjects and a partial response in the third. No clinically significant investigational drug-related hematological and renal toxicity was noted. The most common adverse events noted were diarrhea 2/13(23%), nausea 4/13(30%), fatigue 4/13(30%), hyperglycemia 7/13(53%). Moderate hair loss was seen in 2/13 (15%) patients. Quality of life parameters suggest significant improvement in pain, energy, and shortness of breath in the majority of subjects. Conclusion: Dramatic decreases in tumor burden and a positive impact on quality of life were seen in all of the subjects who received three cycles of AlphaMedixTM at the highest dose tested. In addition, AlphaMedixTM was extremely well tolerated with only mild adverse events, most of which were attributable to the AA solution used for renal protection. This FIH study of AlphaMedixTM illustrates that PRRT with 212Pb is feasible, well-tolerated, and provides substantial reduction in tumor burden to patients with unresectable, metastatic SSTR expressing NETs Citation Format: Izabela Tworowska, Ebrahim S. Delpassand, Julien Torgue, Farah Shanoon, Jason Hurt, Rodolfo Nunez. First-in-human dose escalation of AlphaMedixTM for targeted alpha-emitter therapy of neuroendocrine tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT159.

Pheochromocytomas and paragangliomas represent less than 1% of all endocrine tumors. Approximately 15-20% of these tumors are malignant. The definition of malignancy relies on the presence of metastasis. Metastatic pheochromocytomas and paragangliomas are usually advanced, incurable tumors with limited therapeutic options. About 50-60% of these tumors express the noradrenaline transporter in their cell membranes. Recently, the United States Food and Drug Administration approved high-specific-activity iodine 131 metaiodobenzylguanidine (HSA-I-131-MIBG) for the treatment of metastatic pheochromocytomas and paragangliomas that express the noradrenaline transporter. This review reports the benefits and toxicity of HSA-I-131-MIBG, its physical and dosimetric aspects, and radiation safety precautions, as well as its potential therapeutic value for other malignancies (neuroblastoma, gastroenteropancreatic neuroendocrine tumors, and medullary thyroid carcinoma). A phase 2 clinical trial with HSA-I-131-MIBG reported an impressive clinical benefit rate, acceptable toxicity and long-term benefits. HSA-I-131-MIBG is an effective medication for metastatic pheochromocytomas and paragangliomas that express the noradrenaline transporter.

A 65-year-old man underwent FDG PET/CT for evaluation of vertebral lesions, radiologically suspected to be metastases. The scan showed hypermetabolism in D8 to D9 vertebrae, retroperitoneal lymph nodes, and both the lobes of prostate. Transrectal ultrasound-guided biopsy of prostate was performed with suspicion of prostate malignancy. The biopsy revealed caseating granulomatous lesions in prostate suggestive of tuberculosis. Post antitubercular treatment patient showed excellent clinical response. Possibility of infective pathologies mimicking malignancy should be kept in mind while evaluating hypermetabolic foci seen on PET/CT. Although rare, tuberculosis of prostate needs consideration in differential diagnosis of FDG-avid foci seen in prostate.

Objective: Develop a soft computing model with a graphical interface which will help cardiologists to diagnose the risk of developing hypertension in the next 4 years or, determine the level of hypertension that the patient currently suffers. The use of soft computing such as neural networks, fuzzy logic will provide the system with the ability to perform efficient and rapid diagnoses which will give the expert the confidence to give a reliable diagnosis. Design and method: The design of the graphical interface was made with Python, with the purpose of developing an understandable interface for the specialist doctor in order to incorporate each of the developed modules with fuzzy logic and neural networks, first we have the pressure level module arterial, which is to classify the patient at the current blood pressure level, later on, the nocturnal profile module is used, which will determine whether the patient has any of the different nocturnal classifications such as dipper, no-dipper, extreme dipper or riser. Continuing with the modules, we have the pressure load module which will determine, based on a 24-hour monitoring, the level of pressure load that the patient has, as well as determine the period of time in which the patient is more likely to have a cardiovascular event either day or night. Results: Tests are carried out with different patients, where it can be seen that the GUI yields results correctly, the information is plotted based on the hours the ABPM was placed on the patient, as well as personal information. By entering the information of the risk factors as well as when searching the blood pressure readings of the patients and being simulated by the different artificial neural networks, good results are obtained.Conclusions: The graphical user interface helps to interpret in a simpler way the results obtained from the soft computing techniques used, besides that it was designed in a simple way so that it is easy to use for and interpret for the physicians.

e15175 Background: We retrospectively evaluated the efficacy of PRRT with 111 In-Octreotide (IN) or 117Lu-Octreotate (LU) in the treatment of high grade (HG) mNETS with a positive octreoscan image....