Additional file 1: Supplementary data on the synthesis of BODIPY-BBN, its in-vitro characterization and its in-vivo biodistribution and stability. Figure S1. of Development of a clickable bimodal fluorescent/PET probe for in vivo imaging

Synthesis and analytical data of BODIPY-azide 1. Figure S2. Synthesis of BODIPY-BBN 5 using CuAAC click chemistry. Figure S3. In vitro cell binding study of BODIPY-BBN 5 using GRPr overexpressing PC-3 cells. Figure S4. Quantification of tumor uptake comparing fluorescent imaging as well as gamma-counting. Figure S5. In vivo small animal PET/CT images (60 min) of PC-3 tumor-bearing nude mice after intravenous injection of 18F-BODIPY-BBN 3 (55 ± 10 μCi) in PBS (4 % DMSO, 200 μL). Figure S6. Percent intact fluorescent 19F-BODIPY-BBN in human serum at different time points (0, 15, 30, 45, and 60 min) after incubation at 37 °C

Synthesis and Evaluation of a Novel ⁶⁴Cu- and ⁶⁷Ga-Labeled Neurokinin 1 Receptor Antagonist for <i>in Vivo</i> Targeting of NK1R-Positive Tumor Xenografts

Neurokinin 1 receptor (NK1R) is expressed in gliomas and neuroendocrine malignancies and represents a promising target for molecular imaging and targeted radionuclide therapy. The goal of this study was to synthesize and evaluate a novel NK1R ligand (NK1R-NOTA) for targeting NK1R-expressing tumors. Using a carboxymethyl moiety linked to L-733060 as a starting reagent, NK1R-NOTA was synthesized in a three-step reaction and then labeled with ⁶⁴Cu (or ⁶⁷Ga for <i>in vitro</i> studies) in the presence of CH₃COONH₄ buffer. The radioligand affinity and cellular uptake were evaluated with NK1R-transduced HEK293 cells (HEK293-NK1R) and NK1R nontransduced HEK293 cells (HEK293-WT) and their xenografts. Radiolabeled NK1R-NOTA was obtained with a radiochemical purity of >95% and specific activities of >7.0 GBq/μmol for ⁶⁴Cu and >5.0 GBq/μmol for ⁶⁷Ga. Both ⁶⁴Cu- and ⁶⁷Ga-labeled NK1R-NOTA demonstrated high levels of uptake in HEK293-NK1R cells, whereas co-incubation with an excess of NK1R ligand L-733060 reduced the level of uptake by 90%. Positron emission tomography (PET) imaging showed that [⁶⁴Cu]­NK1R-NOTA had a accumulated rapidly in HEK293-NK1R xenografts and a 10-fold lower level of uptake in HEK293-WT xenografts. Radioactivity was cleared by gastrointestinal tract and urinary systems. Biodistribution studies confirmed that the tumor-to-organ ratios were ≥5 for all studied organs at 1 h p.i., except kidneys, liver, and intestine, and that the tumor-to-intestine and tumor-to-kidney ratios were also improved 4 and 20 h post-injection. [⁶⁴Cu]­NK1R-NOTA is a promising ligand for PET imaging of NK1R-expressing tumor xenografts. Delayed imaging with [⁶⁴Cu]­NK1R-NOTA improves image contrast because of the continuous clearance of radioactivity from normal organs

Additional file 1: Table S1. of Development and exploration of the content validity of a patient-reported outcome measure to evaluate the impact of migraine- the migraine physical function impact diary (MPFID)

Inclusion and Exclusion Criteria for Cognitive Interview Study. (DOCX 27 kb