Small Molecule, Multimodal,[18F]-PET and Fluorescence Imaging Agent Targeting Prostate-Specific Membrane Antigen: First-in-Human Study

[18F]-BF3-Cy3-ACUPA positron emission tomography (PET)/computed tomography (CT) imaging of patient 8. Patient 8 was a candidate for radical prostatectomy (RP) based on prior biopsy and [68Ga]-PSMA-11 imaging. As part of this study, this patient underwent [18F]-BF3-Cy3-ACUPA injection and PET/CT imaging, followed by RP approximately 24 hours later. (A) [68Ga]-PSMA-11 PET maximum intensity projection (MIP) image. (B) [18F]-BF3-Cy3-ACUPA PET MIP image. (C) [68Ga]-PSMA-11 PET/CT image shows localized PSMA+ disease (arrow) but no nodal or distant disease. (D) Similar PET delineations (magenta arrowheads) are observed on the 90-minute postinjection [18F]-BF3-Cy3-ACUPA PET/CT image. Without reinjection, the patient underwent RP 24 hours later (after 18F decayed). (E) Fluorescence images of excised prostate tissue using a first-generation back-table Cy3 fluorescence imaging device. (F) Post-surgical prostate co-registration shows prostate cancer in magnetic resonance imaging (MRI) apparent diffusion coefficient (ADC) image, PET image, and fluorescence image; post-surgical fluorescence image shows a positive margin in the posterior urethra/bladder neck (indicated by a dashed magenta border). Abbreviations: FL = Fluorescence.

A dual-modal PET/near infrared fluorescent nanotag for long-term immune cell tracking

We developed a dual-modal PET/near infrared fluorescent (NIRF) nanoparticle-based imaging agent for non-genomic labeling of human CAR T cells. Since the PET/NIRF nanoparticles did not affect cell viability or cytotoxic functionality and enabled long-term whole-body CAR T cell tracking using PET and NIRF in an ovarian peritoneal carcinomatosis model, this platform is a viable imaging technology to be applied in other cancer models.

CAR T cell accumulation at the tumor site. a, Bioluminescence imaging (BLI) of SKOV3:hCEA(+) in an NSG mouse prior to (t=0) and post adoptive T cell (t=7, 14 days). At t=14 post adoptive cell transfer one major lesion was present (arrow head) b, BLI and PET imaging at 1 h, 14 days post adoptive cell transfer (i.p.) administration of PET/NIRF nanotag-labeled hCEA-redirected CAR T cells. c, Immunofluorescence image of the remaining tumor (red) demonstrates that the majority of CAR T cells (green) were found most prominently in the tumor periphery (scale bar, 1000 mm). d, In another section (box) of the tumor it was found that at t=14 days (p.i.) the PET/NIRF nanotags (yellow) are no longer associated with the hCEA-redirected CAR T cells, but have been released and subsequently taken up by the SKOV3:hCEA(+) cancer cells (scale bars, 100 mm)

One-Step, Rapid, ¹⁸F–¹⁹F Isotopic Exchange Radiolabeling of Difluoro-dioxaborinins: Substituent Effect on Stability and In Vivo Applications

We describe a general method for radiolabeling β-diketone-bearing molecules with fluoride-18. Radiolabeling was carried out via ¹⁸F–¹⁹F isotopic exchange on nonradioactive difluoro-dioxaborinins, which were generated by minimally modifying the β-diketone as a difluoroborate. Radiochemistry was one-step, rapid (<10 min), and high-yielding (>80%) and proceeded at room temperature to accommodate the half-life of F-18 (t_1/2 = 110 min). High molar activities (7.4 Ci/μmol) were achieved with relatively low starting activities (16.4 mCi). An F-18 radiolabeled difluoro-dioxaborinin probe that was simultaneously fluorescent showed sufficient stability for in vivo positron emission tomography (PET)/fluorescence imaging in mice, rabbits, and patients.

Sentinel lymph node imaging using [¹⁸F]-9. A 0.185 MBq radioactivity amount of [¹⁸F]-9 solution was injected into the right rear footpad of mice (n = 3). The radiotracer penetrates into lymphatic vessels and flows to the sentinel lymph nodes automatically, as previously described in many reports.(17) The injection site (red arrow), sentinel lymph node (popliteal, white arrow), and bladder (green arrow) are visible at 2 (a) and 4 h (b) postinjection. (c) PET/MRI imaging of rabbit sentinel (popliteal) lymph nodes (there are two nodes) using [¹⁸F]-9. Injection (7.4 MBq) of [¹⁸F]-9 was made into the right rear paw of a rabbit. The injection site (red arrow) and sentinel lymph node (popliteal, white arrow) are visible 1 h postinjection. (d–f) Fluorescence confirmation of [¹⁸F]-9 in murine sentinel nodes was carried out using 430/520 nm excitation/emission optical filtration, that is, wavelengths that approach the absorption and emission peaks of 9 (see Table 2). (d) Skin on the predissection fluorescent image (node is not visible). (e) Fluorescent image where skin over the sentinel lymph node is removed (node is visible). (f) Overexposed figure (e) (node is more visible). (g) MR image of an enlarged lymph node (1.5–2 cm) in a breast cancer patient. A blue arrow indicates the lymph node. (h) A PET/MR image of a breast cancer patient where the lymph node is confirmed by [¹⁸F]-9 PET. (1.2 GBq (32 mCi) of ¹⁸F^– was used to synthesize [¹⁸F]-6F-Cur-BF₂. A 0.45 GBq (12 mCi) quantity of product was isolated). A blue arrow indicates the lymph node. (i) [¹⁸F]-9 fluorescence image of the same resected lymph node within the lumpectomy tissue-specimen excised from the breast cancer patient. The tissue was imaged under 380–400 nm light illumination. The lymph node is cyan-blue in coloration and is the same node indicated by the blue arrow, as shown in Figure 7g,h