18F-DCFPyL PET/CT in Metastatic Renal Cell Carcinoma.

Targeted molecular imaging with PET uses chemical ligands that are peptides specifically targeting a receptor of interest. Prostate-specific membrane antigen (PSMA) is substantially upregulated in prostate cancer but is also expressed in the neovascular tissue of several malignancies, including renal cell carcinoma (RCC). Radiolabeled peptide targets for PSMA may be helpful in detecting metastatic RCC lesions. We present a case of incidental detection of RCC metastatic disease with PSMA-targeted PET, and we explore potential use for deliberate evaluation of RCC with PSMA-targeted tracers.

Safety and tolerability of Miltuximab® - a first in human study in patients with advanced solid cancers.

OBJECTIVES: Miltuximab® is a chimeric antibody targeting Glypican-1 (GPC-1), a cell surface antigen which is overexpressed in solid cancers. Miltuximab® has shown promising safety and efficacy in radioimmunotherapy models of prostate cancer. This first in human study used Miltuximab® radiolabelled with Gallium-67 ([67Ga]Ga-DOTA-Miltuximab®). The primary study endpoint was to establish safety and tolerability of Miltuximab®. Secondary endpoints were biodistribution, tumour targeting and pharmacokinetic analysis. METHODS: Four cohorts of three patients (9 with advanced prostate cancer, 2 with pancreatic and 1 with bladder cancer) were dosed with 1 mg, ~250 MBq of [67Ga]Ga-DOTA-Miltuximab®. Cohort 1 received [67Ga]Ga-DOTA-Miltuximab® alone, while cohorts 2-4 were pre-infused with increasing doses (3.5, 11.5 and 24 mg, respectively) of unlabelled Miltuximab®-DOTA 1 hour prior to [67Ga]Ga-DOTA-Miltuximab®. Safety and tolerability were assessed by clinical and standard laboratory assessments. Patients underwent whole body gamma-camera scans and SPECT/CT scans up to 144 h post-infusion. Total organ radiation exposure was determined by dosimetry of whole-body gamma scans. RESULTS: The dosing regimen was well tolerated, with no drug-related adverse events observed. Liver and spleen uptake of [67Ga]Ga-DOTA-Miltuximab® was observed. Liver uptake was reduced by pre-infusion of unlabelled Miltuximab®-DOTA. Dosimetry analysis showed a favorable exposure profile. [67Ga]Ga-DOTA-Miltuximab® targeting to tumour sites was observed in two prostate cancer patients who had failed enzalutamide treatment. Higher doses of unlabelled antibody achieved lower liver uptake and increased antibody serum half life. CONCLUSIONS: This study is the first in human for Miltuximab® a first in class antibody targeting GPC-1. The trial met its primary endpoint of safety, demonstrating its potential as a safe and tolerable monoclonal antibody. This safety data, together with targeting to tumour lesions and biodistribution information supports the further clinical development of Miltuximab® as a theranostic agent in a planned Phase I human trial.

Effect of combination inhaled therapy on ventilation distribution measured by SPECT/CT imaging in uncontrolled asthma.

Asthma is characterized by heterogeneous ventilation as measured by three-dimensional ventilation imaging. Combination inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA) treatment response is variable in asthma, and effects on regional ventilation are unknown. Our aims were to determine whether regional ventilation defects decrease after ICS/LABA treatment and whether small airways dysfunction predicts response in uncontrolled asthma. Twenty-two symptomatic participants with asthma underwent single-photon emission computed tomography (SPECT)/CT imaging with Technegas, before and after 8-wk fluticasone/formoterol (1,000/40 µg/day) treatment. Lung regions that were nonventilated, low ventilated, or well ventilated were calculated using an adaptive threshold method and were expressed as a percentage of total lung volume. Multiple-breath nitrogen washout (MBNW) was used to measure diffusion-dependent and convection-dependent small airways function (Sacin and Scond, respectively). Forced oscillation technique (FOT) was used to measure respiratory system resistance and reactance. At baseline and posttreatment, Scond z-score was related to percentage of nonventilated lung, whereas Sacin z-score was related to percentage of low-ventilated lung. Although symptoms, spirometry, FOT, and MBNW improved following treatment, there was no mean change in ventilation measured by SPECT. There was, however, a wide range of changes in SPECT ventilation such that greater percentage of nonventilated lung, older age, and higher Scond predicted a reduction in nonventilated lung after treatment. SPECT ventilation defects are overall unresponsive to ICS/LABA, but the response is variable, with improvement occurring when small airways dysfunction and ventilation defects are more severe. Persistent ventilation defects that correlate with Scond suggest that mechanisms such as non-ICS responsive inflammation or remodeling underlie these defects.NEW & NOTEWORTHY This study provides insights into the mechanisms of high-dose ICS treatment in uncontrolled asthma. Ventilation defects as measured by SPECT/CT imaging respond heterogeneously to increased ICS/LABA treatment, with improvement occurring when ventilation defects and impairment of convection-dependent small airways function are more severe. Persistent correlations between ventilation defects and measures of small airways function suggest the potential presence of ICS nonresponsive inflammation and/or remodeling.

Pituitary incidentaloma found on O-(2-18F-fluoroethyl)-l-tyrosine PET.

Although incidental pituitary findings on (18)F-FDG PET are uncommon, there are several reports published in the literature. It is believed that this is the first reporting of incidental pituitary disease found on O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET) PET imaging. The case provides valuable insight into pathogenesis, diagnostic tools, and related pathology. The power of (18)F-FET in differentiating cerebral metastases and recurrence in patients who had previous surgical and radiation therapy is highlighted, and the incremental benefits over MR imaging and (18)F-FDG PET are outlined. The case represents an uncommon finding on MR imaging and (18)F-FDG PET and a rare finding on (18)F-FET PET.

Risk stratification in heart failure using ¹²³I-MIBG.

Heart failure is a progressive, heterogeneous form of cardiovascular disease that requires treatment to be individualized depending on the presenting symptoms. A decision to use an implantable cardioverter-defibrillator (ICD) is based on chronic heart failure patients presenting with a New York Heart Association classification of II or III and a left ventricular ejection fraction (LVEF) less than or equal to 30%-35%. A large percentage of ICD devices, however, never deliver therapy during their lifetime, and as many as 33% of patients ineligible for an ICD (LVEF > 35%) die of sudden cardiac death. (123)I-metaiodobenzylguanidine ((123)I-MIBG) scintigraphy identifies sympathetic nervous system dysfunction and has been shown to lead to better patient stratification. This article reviews the role of planar (123)I-MIBG global quantitation in improving differentiation of heart failure, regardless of the LVEF, to better identify those in whom an ICD is more likely to reap benefits. It goes on to explore the potential incremental benefit of SPECT-based regional quantitation to risk stratification and provides a case example in which (123)I-MIBG SPECT was used to inform a decision to not use an ICD in a patient eligible under the standard criteria.