Tumor Hypoxia on 18F-fluoromisonidazole Positron Emission Tomography and Distant Metastasis From Head and Neck Squamous Cell Carcinoma.

Importance: Given high rates of locoregional control after definitive management of head and neck squamous cell carcinoma (HNSCC), better methods are needed to project distant metastasis (DM) risk. Tumor hypoxia on 18F-fluoromisonidazole (FMISO) positron emission tomography (PET) is associated with locoregional failure, but data demonstrating an association with DM are limited.

Objective: To determine whether tumor hypoxia on FMISO PET is associated with DM risk after chemoradiotherapy (CRT) for HNSCC.

Lesion Dosimetry for [Lu]Lu-PSMA-617 Radiopharmaceutical Therapy Combined with Stereotactic Body Radiotherapy in Patients with Oligometastatic Castration-Sensitive Prostate Cancer.

A single-institution prospective pilot clinical trial was performed to demonstrate the feasibility of combining [Lu]Lu-PSMA-617 radiopharmaceutical therapy (RPT) with stereotactic body radiotherapy (SBRT) for the treatment of oligometastatic castration-sensitive prostate cancer. Six patients with 9 prostate-specific membrane antigen (PSMA)-positive oligometastases received 2 cycles of [Lu]Lu-PSMA-617 RPT followed by SBRT. After the first intravenous infusion of [Lu]Lu-PSMA-617 (7.

Yttrium-90 Activity Quantification in PET/CT-Guided Biopsy Specimens from Colorectal Hepatic Metastases Immediately after Transarterial Radioembolization Using Micro-CT and Autoradiography.

Purpose: To evaluate the yttrium-90 (Y) activity distribution in biopsy tissue samples of the treated liver to quantify the dose with higher spatial resolution than positron emission tomography (PET) for accurate investigation of correlations with microscopic biological effects and to evaluate the radiation safety of this procedure.

Materials And Methods: Eighty-six core biopsy specimens were obtained from 18 colorectal liver metastases (CLMs) immediately after Y transarterial radioembolization (TARE) with either resin or glass microspheres using real-time Y PET/CT guidance in 17 patients. A high-resolution micro-computed tomography (micro-CT) scanner was used to image the microspheres in part of the specimens and allow quantification of Y activity directly or by calibrating autoradiography (ARG) images.

Outcomes of intraventricular 131-I-omburtamab and external beam radiotherapy in patients with recurrent medulloblastoma and ependymoma.

Purpose: Intraventricular compartmental radioimmunotherapy (cRIT) with 131-I-omburtamab is a potential therapy for recurrent primary brain tumors that can seed the thecal space. These patients often previously received external beam radiotherapy (EBRT) to a portion or full craniospinal axis (CSI) as part of upfront therapy. Little is known regarding outcomes after re-irradiation as part of multimodality therapy including cRIT.

Radioimmunoscintigraphy and Pretreatment Dosimetry of I-Omburtamab for Planning Treatment of Leptomeningeal Disease.

Radiolabeled antibody treatment with I-omburtamab, administered intraventricularly into the cerebrospinal fluid (CSF) space, can deliver therapeutic absorbed doses to sites of leptomeningeal disease. Assessment of distribution and radiation dosimetry is a key element in optimizing such treatments. Using a theranostic approach, we performed pretreatment I-omburtamab imaging and dosimetric analysis in patients before therapy.

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.

TriDFusion (3DF) image viewer.

Background: An open-source, extensible medical viewing platform is described, called the TriDFusion image viewer (3DF). The 3DF addresses many broad unmet needs in nuclear medicine research; it provides a viewer with several tools not available in commercial nuclear medicine workstations, yet invaluable for imaging in research studies.

Results: The 3DF includes an image integration platform to register images from multiple imaging modalities together with delineated volumes of interest (VOIs), structures and dose distributions.

Optimizing Y Particle Density Improves Outcomes After Radioembolization.

Purpose: To determine how particle density affects dose distribution and outcomes after lobar radioembolization.

Methods: Matched pairs of patients, treated with glass versus resin microspheres, were selected by propensity score matching (114 patients), in this single-institution retrospective study. For each patient, tumor and liver particle density (particles/cm) and dose (Gy) were determined.

SUVfdg: A standard-uptake-value (SUV) body habitus normalizer specific to fluorodeoxyglucose (FDG) in humans.

Purpose: To devise a new body-habitus normalizer to be used in the calculation of an SUV that is specific to the PET tracer 18F-FDG.

Methods: A cohort of 481-patients was selected for analysis of 18F-FDG uptake into tissues unaffected by their disease. Among these, 65-patients had only brain concentrations measured and the remaining 416 were randomly divided into an 86-patient test set and a 330-patient training set.

Analysis of capecitabine metabolites in conjunction with digital autoradiography in a murine model of pancreatic cancer suggests extensive drug penetration through the tumor.

Previously published digital autoradiography of H-labeled capecitabine reveals a near-uniform distribution of activity throughout a murine pancreatic model. This is in contrast both to C-labeled gemcitabine, and established expectations, as the dense stroma of pancreatic cancer is understood to inhibit drug penetration. Capecitabine is a pro-drug for 5 FU.

F-18 meta-fluorobenzylguanidine PET imaging of myocardial sympathetic innervation.

Background: I-123 meta-iodobenzylguanidine (MIBG) imaging has long been employed to noninvasively assess the integrity of human norepinephrine transporter-1 and, hence, myocardial sympathetic innervation. Positron-emitting F-18 meta-fluorobenzylguanidine (MFBG) has recently been developed for potentially superior quantitative characterization. We assessed the feasibility of MFBG imaging of myocardial sympathetic innervation.

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.

Application of Community Detection Algorithm to Investigate the Correlation between Imaging Biomarkers of Tumor Metabolism, Hypoxia, Cellularity, and Perfusion for Precision Radiotherapy in Head and Neck Squamous Cell Carcinomas.

The present study aimed to investigate the correlation at pre-treatment (TX) between quantitative metrics derived from multimodality imaging (MMI), including F-FDG-PET/CT, F-FMISO-PET/CT, DW- and DCE-MRI, using a community detection algorithm (CDA) in head and neck squamous cell carcinoma (HNSCC) patients. Twenty-three HNSCC patients with 27 metastatic lymph nodes underwent a total of 69 MMI exams at pre-TX. Correlations among quantitative metrics derived from FDG-PET/CT (SUL), FMSIO-PET/CT (K, k, TBR, and DV), DW-MRI (ADC, IVIM [D, D*, and f]), and FXR DCE-MRI [K, v, and τ]) were investigated using the CDA based on a "spin-glass model" coupled with the Spearman's rank, ρ, analysis.

Optimizing reconstruction parameters for quantitative I-PET in the presence of therapeutic doses of I.

Background: The goal of this work was to determine the quantitative accuracy and optimal reconstruction parameters for I-PET imaging in the presence of therapeutic levels of I. In this effort, images were acquired on a GE D710 PET/CT scanner using a NEMA IEC phantom with spheres containing I and increasing amounts of I activity in the background. At each activity level, two scans were acquired, one with the phantom centered in the field of view (FOV) and one 11.

A phase I trial of sorafenib with whole brain radiotherapy (WBRT) in breast cancer patients with brain metastases and a correlative study of FLT-PET brain imaging.

Purpose: Sorafenib has demonstrated anti-tumor efficacy and radiosensitizing activity preclinically and in breast cancer. We examined sorafenib in combination with whole brain radiotherapy (WBRT) and explored the [18F] 3'deoxy-3'-fluorothymidine (FLT)-PET as a novel brain imaging modality in breast cancer brain metastases.

Methods: A phase I trial of WBRT + sorafenib was conducted using a 3 + 3 design with safety-expansion cohort.

Comparison of FDG and FMISO uptakes and distributions in head and neck squamous cell cancer tumors.

Purpose: Glycolysis is increased by hypoxia, suggesting a possible correlation between the accumulation of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) in malignant tumors and regional hypoxia defined by 1H-1-(3-[18F]fluoro-2-hydroxypropyl)-2-nitroimidazole (FMISO) PET. The aim of this study is to investigate the intra-tumoral spatial distribution and quantitative relationship between FDG and FMISO in a cohort of head and neck squamous cell cancer (HNSCC) patients.

Methods: Twenty HNSCC patients with 20 primary tumors and 19 metastatic lymph nodes (LNs) underwent FDG and FMISO PET within 1 week.

Precision Radiotherapy: Reduction in Radiation for Oropharyngeal Cancer in the 30 ROC Trial.

Background: Patients with human papillomavirus-related oropharyngeal cancers have excellent outcomes but experience clinically significant toxicities when treated with standard chemoradiotherapy (70 Gy). We hypothesized that functional imaging could identify patients who could be safely deescalated to 30 Gy of radiotherapy.

Methods: In 19 patients, pre- and intratreatment dynamic fluorine-18-labeled fluoromisonidazole positron emission tomography (PET) was used to assess tumor hypoxia.

Non-invasive imaging prediction of tumor hypoxia: A novel developed and externally validated CT and FDG-PET-based radiomic signatures.

Background: Tumor hypoxia increases resistance to radiotherapy and systemic therapy. Our aim was to develop and validate a disease-agnostic and disease-specific CT (+FDG-PET) based radiomics hypoxia classification signature.

Material And Methods: A total of 808 patients with imaging data were included: N = 100 training/N = 183 external validation cases for a disease-agnostic CT hypoxia classification signature, N = 76 training/N = 39 validation cases for the H&N CT signature and N = 62 training/N = 36 validation cases for the Lung CT signature.

IntraOmmaya compartmental radioimmunotherapy using I-omburtamab-pharmacokinetic modeling to optimize therapeutic index.

Purpose: Radioimmunotherapy (RIT) delivered through the cerebrospinal fluid (CSF) has been shown to be a safe and promising treatment for leptomeningeal metastases. Pharmacokinetic models for intraOmmaya antiGD2 monoclonal antibody I-3F8 have been proposed to improve therapeutic effect while minimizing radiation toxicity. In this study, we now apply pharmacokinetic modeling to intraOmmaya I-omburtamab (8H9), an antiB7-H3 antibody which has shown promise in RIT of leptomeningeal metastases.

Predicting Gemcitabine Delivery by F-FAC PET in Murine Models of Pancreatic Cancer.

F-FAC (2'-deoxy-2'-F-fluoro-β-d-arabinofuranosylcytosine) has close structural similarity to gemcitabine and thus offers the potential to image drug delivery to tumors. We compared tumor F-FAC PET images with C-gemcitabine levels, established ex vivo, in 3 mouse models of pancreatic cancer. We further modified tumor gemcitabine levels with injectable PEGylated recombinant human hyaluronidase (PEGPH20) to test whether changes in gemcitabine would be tracked by F-FAC.