Table I.
Major Radioisotopes of Interest for the Molecular Imaging of Protein Therapeutics
| Half-life | Coupling chemistry | Availability | Imaged gamma ray energy (keV) | Suitable applications | Notes | |
|---|---|---|---|---|---|---|
| SPECT halogens | ||||||
| I-123 | 13.2 h | Covalent iodination | Commercially available; iodide in NaOH | 159 | SPECT imaging of peptides, small proteins | Ideal energy for most gamma cameras; high photon yield per MBq |
| I-131 | 8.0 days | Covalent iodination | Commercially available; iodide in NaOH | 364 | Cut-and-count studies or SPECT imaging of antibodies over multiple days | Requires heavy-duty collimation and camera shielding; high radiation burden; low photon yield per MBq |
| I-125 | 60 days | Covalent iodination | Commercially available; iodide in NaOH | 35 | Cut-and-count studies, binding assays, autoradiography, small animal imaging | Readily makes high specific activity reagents |
| SPECT radiometals | ||||||
| Tc-99m | 6.0 h | Chelation of a complex (MAG3, HYNIC, histidine repeats) | TcO4-(pertechnetate) from Mo-99 generator; commercially available | 140 | Same-day SPECT imaging of peptides | Historically and commercially important; ubiquitous; inexpensive |
| In-111 | 67.3 h | Chelation (DTPA, DOTA) | Cyclotron; In(III) chloride commercially available | 173, 247 | SPECT imaging of antibodies over multiple days, particularly for internalizing targets where residualization is important | Go-to isotope for residualizing SPECT studies of proteins; incorporated into several diagnostic imaging antibodies |
| Ga-67 | 78.3 h | Chelation (DFO) | Cyclotron; gallium citrate widely available for lung scans | 93, 185, 300 | Not widely adopted, but possible option for SPECT imaging of antibodies over multiple days | Problematic exchange reactions with the abundant transferrin in the body |
| Lu-177 | 6.7 days | Chelation (DOTA) | Cyclotron; Lu(III) chloride commercially available | 113, 208 | RIT with theranostic (simultaneous imaging) potential | Abundant 133 keV beta particles |
| Tl-201 | 12.2 days | None available | Cyclotron; Tl(III) chloride commercially available | 80 | attractive option for dual-isotope studies but no path for protein labeling | Widely discussed as SPECT agent because of clinical ubiquity (heart scans) |
| PET halogens | ||||||
| F-18 | 110 min | Facile complexation with Al3+ and chelation (NOTA, NODA) | Cyclotron; sodium [F18]-fluoride widely available. | 511 | PET imaging of peptides, small proteins | Rapidly evolving technology for protein and peptide labeling applications; excellent image quality from 633 keV positron and maximum possible positron yield per MBq |
| I-124 | 4.2 days | Covalent iodination | Cyclotron; iodide in NaOH | 511 | PET imaging of antibodies over multiple days; particularly for non-internalizing targets where residualization less important | 1.5 and 2.1 MeV positron and prominent 603 keV gamma detract from image quality; low positron yield per MBq |
| PET radiometals | ||||||
| Ga-68 | 68 min | Chelation (DOTA, NOTA, DFO) | Ga(III) chloride typically from parent Ge-68 generator, commercially available | 511 | PET imaging of peptides | Sometimes seen as PET successor to SPECT with Tc-99m, logistic difficulties remain severe |
| Cu-64 | 12.7 h | Chelation (DTPA, DOTA, TETA) | Cyclotron or reactor; Cu(II) chloride. Limited commercial supply | 511 | PET imaging of peptides, small proteins | Some 579 keV betas offer therapeutic potential; relatively low energy 653 keV positrons give very good image quality |
| Zr-89 | 78.4 h | Chelation (DFO) | Cyclotron; Zr(IV) oxalate. Limited commercial supply | 511 | PET imaging of antibodies over multiple days; particularly for internalizing targets where residualization is important | 902 keV positrons give good image quality; 909 keV gamma rays contribute to shielding and dosimetry requirements |
These are grouped by the requisite detection technology, PET, or SPECT, and their element type, halogen, or metal, since that determines the labeling approach. Labeling chemistries are discussed further in the text. Commonly employed chelating groups are listed by their common abbreviations: MAG3 mercaptoacetyltriglycine, HYNIC 6-hydrazinonicotinic acid, DTPA diethylenetriaminepentaacetic acid, DOTA 1,4,7,10-tetraazacyclododecane-N,N′,N″,N′″-tetraacetic acid, NOTA 1,4,7-triazacyclononane-N,N′,N″,-triacetic acid, NODA 1,4,7-triazacyclononane-1,4-diacetate, TETA 1,4,8,11-tetraazacyclotetradecane- N,N′,N″,N′″-tetraacetic acid, DFO desferrioxamine B