Detection of Shortwave-Infrared Cerenkov Luminescence from Medical Isotopes

SWIR CL radioisotope imaging setup and characterization. (A) A dark enclosure was used for all imaging. Mounted on the camera was a 16 or 8 mm ƒ/1.4 SWIR lens. (©2022 Memorial Sloan Kettering Cancer Center. All rights reserved.) (B) Linearity assessment of the camera via ⁶⁸Ga imaged at positions (P1, P2) across the field of view, with P1 + cardboard confirming that detection was not as a result of γ strikes. (C) SWIR gray levels and corresponding ⁶⁸Ga activity (MBq). Linear regression and 95% CIs are shown (Pearson R² = 0.9839, 2-tailed P < 0.0001). SWIR CLI is linearly responsive and quantitative as found with VIS CLI. (D) ³²P SWIR gray-value intensity in relation to exposure time changes. (E) Graphical representation of radioisotope (³²P) SWIR CL emission spectrum from 900 to 1,500 nm, with the blue line representing a 1-phase exponential decay function (R² = 0.9812). Inherent system noise, low photon production, and water absorption prevent detection > 1,400 nm. (F) Descending radioisotope radiance (³²P, ⁶⁸Ga, ⁸⁹Zr, ¹⁸F, and ¹³¹I) corrected for concentration (kBq/μL) and spatial field of view (cm²). Student t test (unpaired, 2-sided) P values are shown. In all cases, mean measurements (red line), SDs (black lines), and individual measurements (n = 90 technical replicates, gray dots) are shown, for radiance comparison negative values were excluded.

Reduced scattering via SWIR CLI (900–1,700 nm) over VIS CLI (400–900 nm). (A) Left, normalized VIS CLI line intensity profiles of a ⁹⁰Y source (Eppendorf, 55.5 MBq in 200 mL of saline) at increasing scattering tissue depths (chicken breast: 0, 10, and 15 mm). Full widths at half maximum increase with scattering tissue depth at 0, 10, and 15 mm with respective full widths at half maximum of 6.38, 13.05, and 33.64 mm. Right, representative VIS CLI images. (B) Left, normalized SWIR CLI line intensity profiles from the phantom setup with full widths at half maximums of 6.24, 6.40, and 7.04 mm. Right, representative SWIR CL images. In all cases, 3 separate line measurements are made from images at each depth (dotted lines), with mean shown (solid line). FWHM = full width at half maximum.

In vitro and ex vivo SWIR CLI (900–1,700 nm) radioisotope sensitivity limit for ⁶⁸Ga radiolabeled SiNPs. (A) SWIR CLI radioisotope in vitro detection limit for ⁶⁸Ga-SiNPs after multiple half-lives. (B) SWIR CLI decay tracking to the limit of detection, linear regression (solid black line, R² = 0.9882) and 95% CIs (solid gray lines) are shown. (C) Ex vivo SWIR CLI limit of detection for ⁶⁸Ga-labeled SiNPs. The detection limit slightly worsens in tissue compared with in vitro imaging (∼140 kBq less sensitive). (D) Linear regression analysis (R² = 0.9923) of ex vivo SWIR CLI of ⁶⁸Ga-labeled SiNPs to limit of detection (403.3 kBq, C), 95% CIs are shown (solid gray lines). Detection limit paw is labeled with a white arrow.