Article Figures & Data
Figures
- FIGURE 1.
Pretargeting with theranostic pair 203Pb and 212Pb. (Left) Decay scheme of in vivo α-generator 212Pb and SPECT-compatible nuclide 203Pb. (Right) Illustration of theranostic pretargeting approach, following concept of reference 9. This figure was created with BioRender. EC = electron capture; t1/2 = half-life.
- FIGURE 2.
Chemical evaluation of Tz compounds. (A) Chemical structures of 4 Tz precursors. (B) Autoradiogram of paper electrophoresis performed with 212Pb-labeled Tz precursors and [212Pb]PbCl2 at pH 7.4. (C) Normalized high-performance liquid chromatography diagrams of free and natPb-labeled Tz compounds (ultraviolet/visible light signal recorded at 254 nm). (D) Radiochemical conversion of Tz precursors (concentration of Tz = 10−6 mol/L, at 37°C) with 203Pb measured via radio–instant thin-layer chromatography.
- FIGURE 3.
Pretargeting study with [203Pb]Pb-DO3A-PEG7-Tz. (A) Biodistribution data of 4 203Pb-labeled Tz tracers (2 nmol, 0.7 MBq) in healthy female nude mice. (B) Results of initial pretargeting study, with study design shown at top and, at bottom, biodistribution data of [203Pb]Pb-DO3A-PEG7-Tz (2 nmol, 0.7 MBq) in mice pretargeted with 5B1-TCO (100 μg, 0.7 nmol), accompanied by SPECT maximum-intensity projections (2 nmol, 18.5 MBq). Bl = bladder uptake; T = tumor uptake.
- FIGURE 4.
212Bi release and dosimetry estimations. (Top) Biodistribution data of 212Bi, measured 15 min after death, and of 212Pb. (Bottom) Estimated relative biological effectiveness–weighted absorbed dose coefficients for [212Pb]Pb-DO3A-PEG7-Tz (in Gy-equivalent per MBq administered) estimated for different assumptions regarding redistribution of 212Pb’s progeny.
- FIGURE 5.
Therapy study: pretargeting with [212Pb]Pb-DO3A-PEG7-Tz. (A) Cerenkov luminescence imaging of 4 arms that received [212Pb]Pb-DO3A-PEG7-Tz (2 nmol) via pretargeting 24 h after injection. (B) Maximum-intensity projections (24 h after injection) of 4 mice (3.7-MBq cohort) injected with [64Cu]Cu-DO3A-PEG7-Tz 1 d after therapy to demonstrate complementary PET imaging. (C) Waterfall plot of fold change of tumor volume for each cohort. (D) Survival probability as function of time after Tz injection (n = 8 per cohort). Bl = bladder uptake; K = kidney uptake; T = tumor uptake.
- FIGURE 6.
Representative histology results. Representative histology of hematoxylin- and eosin-stained kidney (top) and ovarian (bottom) sections of BxPC-3 tumor–bearing female athymic nude mice. (Left) Mice treated with 212Pb. (Right) Control group. Histopathology of kidneys revealed multifocal, minimal-to-mild tubular injury (arrows) affecting approximately 1%–10% of tubules. Control animals showed histologically normal kidneys. Histopathology of treated ovaries revealed diffuse marked ovarian atrophy with complete loss of follicles and corpora lutea.
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