An automated pheochromocytoma and paraganglioma lesion segmentation AI-model at whole-body Ga- DOTATATE PET/CT.

Background: Somatostatin receptor (SSR) targeting radiotracer Ga-DOTATATE is used for Positron Emission Tomography (PET)/Computed Tomography (CT) imaging to assess patients with Pheochromocytoma and paraganglioma (PPGL), rare types of Neuroendocrine tumor (NET) which can metastasize thereby becoming difficult to quantify. The goal of this study is to develop an artificial intelligence (AI) model for automated lesion segmentation on whole-body 3D DOTATATE-PET/CT and to automate the tumor burden calculation. 132 Ga-DOTATATE PET/CT scans from 38 patients with metastatic and inoperable PPGL, were split into 70, and 62 scans, from 20, and 18 patients for training, and test sets, respectively.

Case Series: Variants in Four Patients with Metastatic Pheochromocytoma.

Few reports have highlighted the rare presence of somatic variants in clinically aggressive, metastatic pheochromocytoma/paraganglioma (PCC/PGL); however, none have addressed detailed clinical presentation (including biochemistry and imaging) and management of these patients. Here, we address these clinical features and management based on four PCC patients with somatic variants from our National Institutes of Health PCC/PGL cohort. A total of 192 patients underwent exome sequencing (germline, somatic, or both), and four males were found to have somatic variants (with additional somatic and oncogenic variants in patients 2 and 4, respectively).

Effectiveness of Osteopathic Manipulative Treatment on Hemodynamic and Pulmonary Response in Coronary Artery Bypass Graft Patients: A Meta-Analysis.

In the realm of cardiovascular care, the quest for innovative and holistic approaches to enhance patient outcomes persists. This study analyzes osteopathic manipulative treatment (OMT) and its potential impact on pain intensity, length of hospitalization, respiratory function, and hemodynamic response in patients undergoing coronary artery bypass grafting (CABG). OMT, with its emphasis on physical manipulation of the body's muscles and tissues, presents a potential treatment beyond the realms of conventional post-operative care.

Diagnostic performance of [Ga]DOTATATE PET/CT, [F]FDG PET/CT, MRI of the spine, and whole-body diagnostic CT and MRI in the detection of spinal bone metastases associated with pheochromocytoma and paraganglioma.

Objective: To compare the diagnostic performance of [Ga]DOTATATE PET/CT, [F]FDG PET/CT, MRI of the spine, and whole-body CT and MRI for the detection of pheochromocytoma/paraganglioma (PPGL)-related spinal bone metastases.

Materials And Methods: Between 2014 and 2020, PPGL participants with spinal bone metastases prospectively underwent [Ga]DOTATATE PET/CT, [F]FDG PET/CT, MRI of the cervical-thoracolumbar spine (MRI), contrast-enhanced MRI of the neck and thoraco-abdominopelvic regions (MRI), and contrast-enhanced CT of the neck and thoraco-abdominopelvic regions (CT). Per-patient and per-lesion detection rates were calculated.

Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants: an international expert Consensus statement.

Adult and paediatric patients with pathogenic variants in the gene encoding succinate dehydrogenase (SDH) subunit B (SDHB) often have locally aggressive, recurrent or metastatic phaeochromocytomas and paragangliomas (PPGLs). Furthermore, SDHB PPGLs have the highest rates of disease-specific morbidity and mortality compared with other hereditary PPGLs. PPGLs with SDHB pathogenic variants are often less differentiated and do not produce substantial amounts of catecholamines (in some patients, they produce only dopamine) compared with other hereditary subtypes, which enables these tumours to grow subclinically for a long time.

Early short-term effects on catecholamine levels and pituitary function in patients with pheochromocytoma or paraganglioma treated with [Lu]Lu-DOTA-TATE therapy.

Purpose: While there are reports of treatment-related endocrine disruptions and catecholamine surges in pheochromocytoma/paraganglioma (PPGL) patients treated with [Lu]Lu-DOTA-TATE therapy, the spectrum of these abnormalities in the immediate post-treatment period (within 48 hours) has not been previously evaluated and is likely underestimated.

Methods: The study population included patients (≥18 years) enrolled in a phase 2 trial for treatment of somatostatin receptor (SSTR)-2+ inoperable/metastatic pheochromocytoma/paraganglioma with [Lu]Lu-DOTA-TATE (7.4 GBq per cycle for 1 - 4 cycles).

Phase 1 study of intraventricular I-omburtamab targeting B7H3 (CD276)-expressing CNS malignancies.

Background: The prognosis for metastatic and recurrent tumors of the central nervous system (CNS) remains dismal, and the need for newer therapeutic targets and modalities is critical. The cell surface glycoprotein B7H3 is expressed on a range of solid tumors with a restricted expression on normal tissues. We hypothesized that compartmental radioimmunotherapy (cRIT) with the anti-B7H3 murine monoclonal antibody omburtamab injected intraventricularly could safely target CNS malignancies.

Quantitative PET imaging of the CD4 pool in nonhuman primates.

Purpose: Previous SPECT and PET semi-quantitative in vivo imaging studies in monkeys have demonstrated specific uptake of radiolabeled rhesus recombinant anti-CD4 monoclonal antibody fragment CD4R1-F(ab΄) in the spleen and clusters of lymph nodes (LNs) but yielded conflicting results of imaging the gut CD4 + T-cell pool. Here, using PET dynamic imaging with kinetic analysis, we performed a fully quantitative CD4 imaging in rhesus macaques.

Methods: The biodistributions of [Zr]Zr-CD4R1-F(ab΄) and/or of [Zr]Zr-ibalizumab were performed with static PET scans up to 144 h (6 days) post-injection in 18 rhesus macaques with peripheral blood CD4 + T cells/μl ranging from ~ 20 to 2400.

Performances of Functional and Anatomic Imaging Modalities in Related Metastatic Pheochromocytoma and Paraganglioma.

The study identifies the importance of positron emission tomographic (PET) and anatomic imaging modalities and their individual performances in detecting succinate dehydrogenase A (-related metastatic pheochromocytoma and paraganglioma (PPGL). The detection rates of PET modalities-Ga-DOTATATE, F-FDG, and F-FDOPA-along with the combination of computed tomography (CT) and magnetic resonance imaging (MRI) are compared in a cohort of 11 patients with metastatic PPGL in the setting of a germline mutation. The imaging detection performances were evaluated at three levels: overall lesions, anatomic regions, and a patient-by-patient basis.

Treatment of Patients with Acute Myeloid Leukemia with the Targeted Alpha-Particle Nanogenerator Actinium-225-Lintuzumab.

Purpose: The anti-CD33 antibody lintuzumab has modest activity against acute myeloid leukemia (AML). To increase its potency, lintuzumab was conjugated to actinium-225 (225Ac), a radionuclide yielding 4 α-particles. This first-in-human, phase I trial was conducted to determine the safety, pharmacology, and biological activity of 225Ac-lintuzumab.

Biodistribution and Radiation Dosimetry of Intraperitoneally Administered I-Omburtamab in Patients with Desmoplastic Small Round Cell Tumors.

The aim of this study was to assess the pharmacokinetics, biodistribution, and radiation dosimetry of I-omburtamab administered intraperitoneally in patients with desmoplastic small round cell tumor. Eligible patients diagnosed with desmoplastic small round cell tumor with peritoneal involvement were enrolled in a phase I trial of intraperitoneal radioimmunotherapy with I-omburtamab. After thyroid blockade and before radioimmunotherapy, patients received approximately 74 MBq of I-omburtamab intraperitoneally.

Systemic Radiopharmaceutical Therapy of Pheochromocytoma and Paraganglioma.

Whereas benign pheochromocytomas and paragangliomas are often successfully cured by surgical resection, treatment of metastatic disease can be challenging in terms of both disease control and symptom control. Fortunately, several options are available, including chemotherapy, radiation therapy, and surgical debulking. Radiolabeled metaiodobenzylguanidine (MIBG) and somatostatin receptor imaging have laid the groundwork for use of these radiopharmaceuticals as theranostic agents.

Sporadic Primary Pheochromocytoma: A Prospective Intraindividual Comparison of Six Imaging Tests (CT, MRI, and PET/CT Using Ga-DOTATATE, FDG, F-FDOPA, and F-FDA).

. Recent professional society guidelines for radionuclide imaging of sporadic pheochromocytoma (PHEO) recommend F-fluorodihydroxyphenylala-nine (F-FDOPA) as the radiotracer of choice, deeming Ga-DOTATATE and FDG to be second- and third-line agents, respectively. An additional agent, F-fluorodopamine (F-FDA), remains experimental for PHEO detection.

Imaging of Pheochromocytoma and Paraganglioma.

Imaging plays a critical role in the management of pheochromocytomas and paragangliomas and often guides treatment. The discovery of susceptibility genes associated with these tumors has led to better understanding of clinical and imaging phenotypes. Functional imaging is of prime importance because of its sensitivity and specificity in subtypes of pheochromocytoma and paraganglioma.

Monitoring Immune Activation with Whole-Body Fluorodeoxyglucose-Positron-Emission Tomography in Simian Immunodeficiency Virus-Infected Rhesus Macaques.

This study aimed to assess immune activation in tissues by measuring glucose metabolism with F-fluorodeoxyglucose (FDG) and investigate the associations of various peripheral markers of disease progression with initiation and interruption of combination antiretroviral therapy in SIV-infected rhesus macaques (). Mixed-effect linear models revealed a significant inverse association of peripheral blood CD4 T cell counts ( < 0.01) and a direct association of plasma viral load ( < 0.

High-Specific-Activity-I-MIBG versus Lu-DOTATATE Targeted Radionuclide Therapy for Metastatic Pheochromocytoma and Paraganglioma.

Targeted radionuclide therapies (TRT) using I-metaiodobenzylguanidine (I-MIBG) and peptide receptor radionuclide therapy (Lu or Y) represent several of the therapeutic options in the management of metastatic/inoperable pheochromocytoma/paraganglioma. Recently, high-specific-activity-I-MIBG therapy was approved by the FDA and both Lu-DOTATATE and I-MIBG therapy were recommended by the National Comprehensive Cancer Network guidelines for the treatment of metastatic pheochromocytoma/paraganglioma. However, a clinical dilemma often arises in the selection of TRT, especially when a patient can be treated with either type of therapy based on eligibility by MIBG and somatostatin receptor imaging.

Case Report: Primary Hypothyroidism Associated With Lutetium 177-DOTATATE Therapy for Metastatic Paraganglioma.

Background: Lutetium 177 (Lu) - DOTATATE is a form of peptide receptor radionuclide therapy (PRRT) utilized in the treatment of neuroendocrine tumors. Data on Lu-DOTATATE-induced thyroid dysfunction is limited.

Case Description: A 29-year-old male with  positive metastatic paraganglioma enrolled under the Lu-DOTATATE trial (NCT03206060) underwent thyroid function test (TFT) evaluation comprised of thyroid stimulating hormone (TSH) and free thyroxine (FT4) immunoassay measurements per protocol prior to Lu-DOTATATE therapy.

Overcoming Barriers to Radiopharmaceutical Therapy (RPT): An Overview From the NRG-NCI Working Group on Dosimetry of Radiopharmaceutical Therapy.

Radiopharmaceutical therapy (RPT) continues to demonstrate tremendous potential in improving the therapeutic gains in radiation therapy by specifically delivering radiation to tumors that can be well assessed in terms of dosimetry and imaging. Dosimetry in external beam radiation therapy is standard practice. This is not the case, however, in RPT.

B7H3-Directed Intraperitoneal Radioimmunotherapy With Radioiodinated Omburtamab for Desmoplastic Small Round Cell Tumor and Other Peritoneal Tumors: Results of a Phase I Study.

Purpose: Desmoplastic small round cell tumor (DSRCT), a rare sarcoma of adolescents/young adults primarily involving the peritoneum, has a long-term survival of < 20% despite aggressive multimodality treatment. B7H3 is expressed on DSRCT cell surface, providing a target for antibody-based immunotherapy.

Patients And Methods: In this phase I study, we evaluated the safety, pharmacokinetics, and biodistribution of intraperitoneal (IP) radioimmunotherapy (RIT) with the anti-B7H3 murine monoclonal antibody I-omburtamab in patients with DSRCT or other B7H3-expressing tumors involving the peritoneum.

Identification of HER2-Positive Metastases in Patients with HER2-Negative Primary Breast Cancer by Using HER2-targeted Zr-Pertuzumab PET/CT.

Background Human epidermal growth factor receptor 2 (HER2)-targeted therapies are successful in patients with HER2-positive malignancies; however, spatial and temporal heterogeneity of HER2 expression may prevent identification of optimal patients for these therapies. Purpose To determine whether imaging with the HER2-targeted PET tracer zirconium 89 (Zr)-pertuzumab can depict HER2-positive metastases in women with HER2-negative primary breast cancer. Materials and Methods From January to June 2019, women with biopsy-proven HER2-negative primary breast cancer and biopsy-proven metastatic disease were enrolled in a prospective clinical trial ( NCT02286843) and underwent Zr-pertuzumab PET/CT for noninvasive whole-biopsy evaluation of potential HER2-positive metastases.

Y-Daclizumab (Anti-CD25), High-Dose Carmustine, Etoposide, Cytarabine, and Melphalan Chemotherapy and Autologous Hematopoietic Stem Cell Transplant Yielded Sustained Complete Remissions in 4 Patients with Recurrent Hodgkin's Lymphoma.

Despite advances in therapy of Hodgkin's lymphoma (HL), a proportion of patients will not respond or relapse. The authors had previously identified CD25, IL-2Rα, as a target for systemic radioimmunotherapy of HL since most normal cells do not express CD25, but it is expressed by a minority of Hodgkin/Reed-Sternberg (HRS) cells and most Tregs rosetting around HRS cells. This was a single institution, nonrandomized, open-label phase I/II trial of radiolabeled Y-daclizumab, an anti-CD25 monoclonal antibody, BEAM (carmustine, etoposide, cytarabine, and melphalan) conditioning treatment followed by autologous hematopoietic stem cell transplant (ASCT).

18F-FDG PET Imaging Features of Patients With Autoimmune Lymphoproliferative Syndrome.

Introduction: Autoimmune lymphoproliferative syndrome (ALPS) is a rare immune dysregulatory condition, usually presenting in childhood with massive lymphadenopathy, splenomegaly, and an increased incidence of lymphoma. Methods to differentiate between benign ALPS adenopathy and lymphoma are needed. To this end, we evaluated the usefulness of FDG PET.

Retooling a Blood-Based Biomarker: Phase I Assessment of the High-Affinity CA19-9 Antibody HuMab-5B1 for Immuno-PET Imaging of Pancreatic Cancer.

Purpose: In patients with cancer who have an abnormal biomarker finding, the source of the biomarker in the bloodstream must be located for confirmation of diagnosis, staging, and therapy planning. We evaluated if immuno-PET with the radiolabeled high-affinity antibody HuMab-5B1 (MVT-2163), binding to the cancer antigen CA19-9, can identify the source of elevated biomarkers in patients with pancreatic cancer.

Patients And Methods: In this phase I dose-escalating study, 12 patients with CA19-9-positive metastatic malignancies were injected with MVT-2163.

Biodistribution and Dosimetry of Intraventricularly Administered I-Omburtamab in Patients with Metastatic Leptomeningeal Tumors.

Radiation dose estimations are key for optimizing therapies. We studied the role of I-omburtamab (8H9) given intraventricularly in assessing the distribution and radiation doses before I-omburtamab therapy in patients with metastatic leptomeningeal disease and compared it with the estimates from cerebrospinal fluid (CSF) sampling. Patients with histologically proven malignancy and metastatic disease to the central nervous system or leptomeninges who met eligibility criteria for I-omburtamab therapy underwent immuno-PET imaging with I-8H9 followed by I-8H9 antibody therapy.