New Developments in Dual-Labeled Molecular Imaging Agents

Abstract

Intraoperative detection of tumors has had a profound impact on how cancer surgery is performed and addresses critical unmet needs in surgical oncology. Tumor deposits, margins, and residual cancer can be imaged through the use of fluorescent contrast agents during surgical procedures to complement visual and tactile guidance. The combination of fluorescent and nuclear contrast into a multimodality agent builds on these capabilities by adding quantitative, noninvasive nuclear imaging capabilities to intraoperative imaging. This review focuses on new strategies for the development and evaluation of targeted dual-labeled molecular imaging agents while highlighting the successful first-inhuman application of this technique.

Trending: Radioactive and Fluorescent Bimodal/Hybrid Tracers as Multiplexing Solutions for Surgical Guidance

“…Pioneering clinical trials with hybrid tracers (15,16) have helped to overcome some reservations among researchers and surgeons with regard to this innovative surgical guidance concept. Table 1 illustrates that the field has moved forward over the years and underscores that different combinations of isotopes and dyes can be used in the clinical setting.…”

“…The literature on the preclinical use and assessment of hybrid tracers can be considered substantial. After the pioneering review by Culver et al (22), numerous others have addressed the topic (5,16,(23)(24)(25)(26). Besides oncologic imaging targets, such as human epidermal growth factor receptor 2, prostate-specific membrane antigen, carcinoembryonic antigen, a 5 b 3 , somatostatin receptor 2, and chemokine receptor 4 or sentinel node imaging, applications in, for example, infectious diseases have been reported.…”

“…In preclinical studies, a plurality of imaging labels has been incorporated into hybrid tracer designs: radiolabels (e.g., 99m Tc, 111 In, 18 F, 68 Ga, and 89 Zr) and fluorescent labels (e.g., fluorescein isothiocyanate [FITC], cyanine dye CY5, 800CW, ZW800, and ICG). In an attempt to cover the essence of these initiatives, we refer to key review articles according to their chemical scaffold: peptides (24,25), single-domain antibodies (26), antibodies (16,24), and nanoparticles and bionanoparticles (5). From this combined literature we concluded that there are essentially 3 ways of creating a hybrid tracer: The first is functionalization of large proteins and nanoparticles, generally occurring with separate radiolabels and fluorescent labels.…”

Development of a drug–device combination for fluorescence-guided surgery in neuroendocrine tumors

“…Furthermore, the most significant impact of dual labeling may occur within drug optimization as novel NIRF dyes with superior pharmacokinetic and optical properties continue to emerge. 48…”

Site-Specific Dual-Labeling of a VHH with a Chelator and a Photosensitizer for Nuclear Imaging and Targeted Photodynamic Therapy of EGFR-Positive Tumors

“…The radiometal can be used for nuclear imaging to localize and quantify target expression preoperatively, and for radioguidance to the tumor intraoperatively. Fluorescence imaging and tPDT can be used during surgery as well, to ensure complete resection and eradication of all tumor cells, respectively [ 17 , 18 , 19 , 20 ]. Besides application in the clinic, the presence of a radiometal is also advantageous for performing relatively easy and quantitative biodistribution studies of small compounds in vivo.…”