Initial evaluation of [18F]-FACBC for PET imaging of multiple myeloma.

RATIONALE: Multiple myeloma (MM) cells synthesize large amounts of paraproteins, making radiolabeled amino acids promising candidates for PET imaging of MM patients. METHODS: We compare tumor uptake of the two amino acid analogs [18F]-fluoroethyltyrosine and [18F]-FACBC in a MM xenograft model and show the feasibility of PET imaging with [18F]-FACBC in a MM patient. RESULTS: Preclinically [18F]-FACBC showed superior performance, mainly due to the uptake via the ASC-system. In a subsequent proof-of-concept investigation [18F]-FACBC PET was performed in a MM patient. It allowed identification of both lesions with and without CT correlate (SUVmean 8.0 or 7.9) based on higher uptake compared to normal bone marrow (SUVmean 5.7). Bone signal was elevated compared to non-MM patients, and, thus [18F]-FACBC potentially allows the assessment of bone marrow infiltration. CONCLUSION: The FDA/EMA approved PET agent [18F]-FACBC is promising for imaging MM and should be further evaluated in prospective clinical studies.

Bacterial encapsulins as orthogonal compartments for mammalian cell engineering.

We genetically controlled compartmentalization in eukaryotic cells by heterologous expression of bacterial encapsulin shell and cargo proteins to engineer enclosed enzymatic reactions and size-constrained metal biomineralization. The shell protein (EncA) from Myxococcus xanthus auto-assembles into nanocompartments inside mammalian cells to which sets of native (EncB,C,D) and engineered cargo proteins self-target enabling localized bimolecular fluorescence and enzyme complementation. Encapsulation of the enzyme tyrosinase leads to the confinement of toxic melanin production for robust detection via multispectral optoacoustic tomography (MSOT). Co-expression of ferritin-like native cargo (EncB,C) results in efficient iron sequestration producing substantial contrast by magnetic resonance imaging (MRI) and allowing for magnetic cell sorting. The monodisperse, spherical, and iron-loading nanoshells are also excellent genetically encoded reporters for electron microscopy (EM). In general, eukaryotically expressed encapsulins enable cellular engineering of spatially confined multicomponent processes with versatile applications in multiscale molecular imaging, as well as intriguing implications for metabolic engineering and cellular therapy.

Calcium Sensor for Photoacoustic Imaging.

We introduce a selective and cell-permeable calcium sensor for photoacoustics (CaSPA), a versatile imaging technique that allows for fast volumetric mapping of photoabsorbing molecules with deep tissue penetration. To optimize for Ca2+-dependent photoacoustic signal changes, we synthesized a selective metallochromic sensor with high extinction coefficient, low quantum yield, and high photobleaching resistance. Micromolar concentrations of Ca2+ lead to a robust blueshift of the absorbance of CaSPA, which translated into an accompanying decrease of the peak photoacoustic signal. The acetoxymethyl esterified sensor variant was readily taken up by cells without toxic effects and thus allowed us for the first time to perform live imaging of Ca2+ fluxes in genetically unmodified cells and heart organoids as well as in zebrafish larval brain via combined fluorescence and photoacoustic imaging.