Supplementary Table S5. Region of interest analysis data reported as %ID/cc of the [89Zr]PEG-DFB1-TLZ3 on on different subcutaneous tumors from Day 1-4 post injection. (n = 4)

Supplementary Figure S13. Autoradiographic images and H&E staining images of subcutaneous CT26 tumor sections from day 1 to day 4 post injection of 89Zr labeled nanocarriers. *Indicate the presence of necrosis.

Supplementary Figure S4. Coronal μPET/CT fusion and MIP images obtained at 18 h, 48 h, 72 h, and 96 h following administration of 150-170 μCi of 89Zr labeled nanocarriers in nude mice bearing 22rv1 subcutaneous tumors over left flanks.

Supplementary Figure S2. Pilot PET/CT studies in prostate, pancreatic, and colorectal cancer models to measure the enhanced permeability retention effect using [89Zr]PEG-DFB1-TLZ3.

Infectious diseases are a major cause of morbidity and mortality worldwide. With the increasing frequency of antibiotic resistance, efficient and noninvasive diagnostic methods are more important than ever. In this report, we interrogate the use of several intravenously administered, bacteria-specific, 13C-enriched metabolites whose conversion to [13C]-CO2 can be detected via a portable and inexpensive method, namely nondispersive infrared (NDIR) spectroscopy. The enriched metabolites [U-13C]-maltose, [U-13C]-maltotriose, d-[U-13C]-mannitol, and l-[U-13C]-arabinose were metabolized to [13C]-CO2 by several pathogens in vitro, while showing minimal [13C]-CO2 production in uninfected mice. We further demonstrated that myositis, bacteremia, pneumonia, and osteomyelitis could be detected in vivo using one or more 13C-enriched metabolites. Additionally, in a model of Escherichia coli myositis, [13C]-CO2 production correlated with bacterial burden following ceftriaxone therapy, showing that exhaled [13C]-CO2 could be employed to monitor antimicrobial efficacy. Finally, [13C]-CO2 production by Staphylococcus aureus clinical isolates treated with [U-13C]-maltose was correlated with the performance of its cognate PET tracer [2-18F]-maltose, suggesting that [13C]-CO2 breath testing could predict the performance of pathogen-targeted positron emission tomography (PET) tracers in vivo. [13C]-CO2 breath testing using an expanded metabolite toolbox and on-site detection tools represents a unique and complementary method to identify bacterial infection in clinical practice.

Supplementary Table S4. Region of interest analysis data reported as %ID/cc of the [89Zr]PEG-DFB4 on different subcutaneous tumors from Day 1-4 post injection. (n = 4)

Supplementary Figure S23. Organ biodistribution presented in (left) %ID/g, and (right) %ID/organ of 89Zr labeled nanocarriers in nude mice inoculated with 22rv1 cells via intracardiac injection at 72 h postinjection. (n = 4, mean ± SD)

Supplementary Figure S21. Autoradiographic images and H&E staining images of metastatic tumor, and kedney sections from day 1 to day 4 post injection of [89Zr]PEG-DFB1-TLZ3 in nude mice inoculated with 22rv1 cells in the left kidney capsule. (NA = Data not available)

Supplementary Table S3. Organ biodistribution data in %ID/Organ tissue for [89Zr]PEG-DFB1-TLZ3 at 72 h in mice model bearing different subcutaneous tumors. (n = 4)

Supplementary Table S1. Region of interest analysis data reported as %ID/cc of the [89Zr]PEG-DFB1-TLZ3 on on different subcutaneous tumors on 24 h and 72 h post injection. (n = 4)

Supplementary Table S14. Comparison of influx and efflux rates of [89Zr]PEG-DFB4 and [89Zr]PEG-DFB1-TLZ3 conjugates in different subcutaneous tumor models (n = 4, mean ± SD). *Prior published data.6

Supplementary Figure S12. Autoradiographic images and H&E staining images of subcutaneous 22rv1 tumor sections from day 1 to day 4 post injection of 89Zr labeled nanocarriers. *Indicate the presence of necrosis.

Supplementary Figure S18. BLI of all mice in the cohort inoculated with 22rv1-Luc cells in the left kidney capsule that demonstrate prominent signal of metastatic tumors at the neck and thigh region on the day of [89Zr]PEG-DFB1-TLZ3 injection. Black arrows indicate the presence of metastatic tumors.

Supplementary Figure S7. Coronal μPET/CT fusion and MIP images obtained at 24 h, 48 h, 72 h, and 96 h following administration of 150-170 μCi of 89Zr labeled nanocarriers in nude mice bearing LTL-610 patient derived xenograft (PDX) of tumors over left flanks.

Supplementary Figure S10. Organ biodistribution presented in (left) %ID/g, and (right) %ID/organ for 89Zr labeled nanocarriers in nude mice bearing LTL-545 patient derived xenograft (PDX) of tumors at 96 h postinjection. (n = 4, mean ± SD)

Supplementary Table S11. Organ biodistribution analysis data in %ID/Organ tissue for 89Zr labeled nanocarriers at 96 h in mice model bearing LTL-545 subcutaneous tumors. (n = 4)

Supplementary Figure S1. (a) Zeta potential of the StarPEG conjugates PEG-DFB4 and PEG-DFB1-TLZ3 with an average surface charge of -4.04±0.21 mV and -1.41±0.22 mV, respectively (n = 3). (b) TEM images of PEG-DFB4 and PEG-DFB1-TLZ3 showing the formation of nanoparticles in the range of 10 to 15 nm. TEM samples were prepared by dropcasting the water solution (0.25 mg/mL) of respective StarPEG on carbon coated copper grid of 200 mesh.

Supplementary Figure S14. Autoradiographic images and H&E staining images of PDX LTL-545 tumor sections from day 1 to day 4 post injection of 89Zr labeled nanocarriers.

Supplementary Figure S6. Coronal μPET/CT fusion and MIP images obtained at 24 h, 48 h, 72 h, and 96 h following administration of 150-170 μCi of 89Zr labeled nanocarriers in nude mice bearing LTL-545 patient derived xenograft (PDX) of tumors over left flanks.