Table 3.
Target | Chelator | NIRF Dye | Radionuclide | Reaction buffer | pH | Heating conditions | Dose prepared or administered | Optical stability (HPLC) | Spectral properties evaluated | Conclusions | Refs |
---|---|---|---|---|---|---|---|---|---|---|---|
Integrin αvβ3 | DTPA | IRDye 800CW | In-111 | 0.1 M NaOAc | 5.5 | 25°C, 15 min | Administered | NG | Ex/Em spectra | • Provided a comparative assessment of optical intensified charge-coupled device camera image in comparison with nuclear imaging | [37, 62] |
• Amount: 5 nmol | • Showed optical imaging is highly sensitive to photons emanating from superficial depths | ||||||||||
• Activity: 3.3 MBq | • Demonstration of feasibility of nuclear/NIRF imaging with a single agent and proposed path for translation of NIR fluorescence through dual-labeling | ||||||||||
Integrin αvβ3 | DFO | Cypate | Cold Ga, In, Cu | Water/acetonitrile | NG | NG | NG | NG | Extinction coefficient | • Developed a multifunctional imaging probe for NIRF imaging, delivery of DFO to tumor cells, and potential chelation of radiometals | [38] |
Ex/Em spectra | • Demonstrated that a targeted therapeutic that could be monitored by multimodal imaging | ||||||||||
• Developed a novel platform for optimization of multimodal imaging agents | |||||||||||
Integrin αvβ3 | DOTA | Cypate | In-111 | 0.1 M NaOAc | 5.5 | 80°C, 1 h | Administered | NG | NG | • Developed a DOTA/NIRF RGD analog for dual-labeling | [39] |
• Amount: 140–800 pmol | • Agent was prepared in high specific activity and has potential use with different radiometals due to presence of DOTA as chelator | ||||||||||
• Activity: 1.5–7.4 MBq | • Tumors visualization by both nuclear/NIRF imaging concurred with reports from earlier studies. | ||||||||||
SSTR | DOTA | Cypate | Cu-64, Lu-177 | 0.1 M NaOAc | 5.5 | 25°C; 80°C for 80 min | Prepared (64Cu) | NG | Ex/Em spectra | • Developed a dual-labeled SSTR targeting agent for nuclear/NIRF imaging | [46] |
• Amount: 1 nmol | Quantum yield (performed after cold-labeling) | • Utilized therapeutic radionuclides in multi-modal monomolecular imaging agent (MOMIA) dual-labeling strategy | |||||||||
• Activity: 12.3 MBq | • Fluorescent properties were retained after labeling with metal. | ||||||||||
Administered (64Cu) | • Excellent agreement between the optical and radiochemical biodistribution demonstrates the utility of MOMIA platform | ||||||||||
• Amount: 12 pmol | |||||||||||
• Activity: 0.2 MBq | |||||||||||
MMP | DOTA | IRDye 800CW | Cu-64 | 0.1 M NaOAc | 6 | 50°C, 1 h | Prepared | Yes | NG | • Application of multimodal imaging to detect new bone formation in vivo | [64] |
• Amount: 6–35 nmol | • PET/NIRF imaging served as an early indicator of new bone formation prior to anatomical changes being detectable by CT | ||||||||||
• Activity: 37–74 MBq | |||||||||||
Administered | |||||||||||
• Amount: 6 nmol | |||||||||||
• Activity: 7.4 MBq | |||||||||||
MMP | DOTA | IRDye 800CW | Ga-68 | 0.1 M NaOAc | 4 | 95°C, 10 min | Prepared | Yes | Extinction coefficient | • Developed a dual-labeled nuclear/NIRF imaging agent using generator-produced 68Ga | [49] |
• Amount: 35 nmol | Quantum yield (performed after radiolabeling) | • Chemical, radiochemical, and optical stability was shown | |||||||||
• Activity: 55.5 MBq | • In vivo PET/NIRF imaging demonstrated feasibility of using 68Ga with NIRF as a dual-labeling strategy for peptides or small molecules | ||||||||||
Administered | |||||||||||
• Amount: 6 nmol | |||||||||||
• Activity: 7.4 MBq | |||||||||||
Interleukin-11 receptor-α | DTPA | IR783 | In-111 | 0.1 M NaOAc | NG | 25°C, 30 min | Administered | NG | Ex/Em spectra | • Applied dual-labeling strategy for nuclear/NIRF imaging of IL-11Rα without altering targeting capability of peptide | [50] |
• Amount: 2 nmol | • 111In chelation showed no quenching of fluorescence | ||||||||||
• Preliminary imaging by optical and nuclear methods were consistent | |||||||||||
Caspase-3 | DOTA | LS-276 | Cu-64 | 0.1 M NH4OAc | 5.5 | 60°C, 30 min | Prepared | NG | NG | • Developed a multimodal imaging agent activated by enzymatic cleavage | [51] |
• Amount: 1.3 nmol | • Results demonstrate the feasibility of using radionuclide imaging for localizing and quantifying the distribution of molecular probes and optical imaging for reporting the functional status of diagnostic enzymes | ||||||||||
• Activity: 17.4 MBq | |||||||||||
Hydroxyapatiteb | N3S | IRDye 800CW | Tc-99 m | DMSO | NG | 25°C, 1 h | Prepared | NG | Ex/Em spectra | • Developed a bisphosphonate-based dual modality nuclear/NIRF contrast agent for detecting breast cancer microcalcifications | [52] |
• Specific activity: 6,250 Ci/mmol | Quantum yield | • Described 99mTc labeling effects on spectral properties of IRDye 800CW | |||||||||
Administered | • Demonstrated nearly identical total body clearance compared to the nuclear “gold standard” 99mTc-MDP | ||||||||||
• Amount: 25 nmol | |||||||||||
• Activity: 18.5 MBq |
a NG not given
bUsed a nonpeptide targeting moiety