Dual mode fluorescent (18)F-PET tracers: efficient modular synthesis of rhodamine-[cRGD]2-[(18)F]-organotrifluoroborate, rapid, and high yielding one-step (18)F-labeling at high specific activity, and correlated in vivo PET imaging and ex vivo fluorescence.

The design of dual mode fluorescent-PET peptidic tracers that can be labeled with [(18)F]fluoride at high specific activity and high yield has been challenged by the short half-life of (18)F and its aqueous indolence toward nucleophilic displacement, that often necessitates multistep reactions that start with punctiliously dry conditions. Here we present a modular approach to constructing a fluorescent dimeric peptide with a pendant radioprosthesis that is labeled in water with [(18)F]fluoride ion in a single, user-friendly step. The modular approach starts with grafting a new zwitterionic organotrifluoroborate radioprosthesis onto a pentaerythritol core with three pendent alkynes that enable successive grafting of a bright fluorophore (rhodamine) followed by two peptides (cylcoRGD). The construct is labeled with [(18)F]fluoride via isotope exchange within 20 min in a single step at high specific activity (>3 Ci/µmol) and in good yield to provide 275 mCi and high radiochemical purity. Neither drying of the [(18)F]fluoride ion solution nor HPLC purification of the labeled tracer is required. Facile chemical synthesis of this dual mode tracer along with a user-friendly one-step radiolabeling method affords very high specific activity. In vivo PET images of the dual mode tracer are acquired at both high and low specific activities. At very high specific activity, i.e., 3.5 Ci/µmol, tumor uptake is relatively high (5.5%ID/g), yet the associated mass is below the limits of fluorescent detection. At low specific activity, i.e., 0.01 Ci/µmol, tumor uptake in the PET image is reduced by approximately 50% (2.9%ID/g), but the greater associated mass enables fluorescence detection in the tumor. These data highlight a facile production of a dual mode fluorescent-PET tracer which is validated with in vivo and ex vivo images. These data also define critical limitations for the use of dual mode tracers in small animals.

An organotrifluoroborate for broadly applicable one-step 18F-labeling.

A new zwitterionic organotrifluoroborate is appended to three radiosynthons that afford undergo facile bioconjugation to several clinically relevant peptides and one enzyme inhibitor. Molecularly complex bioconjugates are (18)F-labeled in a single aqueous step in rapid time (<15 min) without HPLC purification to afford tracers in good yields (>200 mCi, 20-40%) at high specific activity (≥3 Ci/µmol) and at >98% purity. PET imaging shows in vivo stability and tumor uptake.

Maintaining Mobility in a Patient Who Is Pregnant and Has COVID-19 Requiring Extracorporeal Membrane Oxygenation: A Case Report.

OBJECTIVE: Mobilization while receiving life support interventions, including mechanical ventilation and extracorporeal membrane oxygenation (ECMO), is a recommended intensive care unit (ICU) intervention to maintain physical function. The purpose of this case report is to describe a novel approach to implementing early mobility interventions for a patient who was pregnant and receiving ECMO while continuing necessary infectious disease precautions because of diagnosed coronavirus disease-19 (COVID-19). METHODS: A 27-year-old woman who was pregnant was admitted to the ICU with COVID-19 and rapidly developed acute respiratory failure requiring 9 days of ECMO support. After a physical therapist consultation, the patient was standing at the bedside by hospital day 5 and ambulating by hospital day 9. RESULTS: The patient safely participated in physical therapy during ICU admission and was discharged to home with outpatient physical therapy follow-up after 14 days of hospitalization. CONCLUSION: Early mobility is feasible during ECMO with COVID-19, and active participation in physical therapy, including in-room ambulation, may facilitate discharge to home. Innovative strategies to facilitate routine activity in a patient who is critically ill with COVID-19 require an established and highly trained team with a focus on maintaining function. IMPACT: Early mobility while intubated, on ECMO, and infected with COVID-19 is feasible while adhering to infectious disease precautions when it is performed by an experienced interdisciplinary team.