Table 1.
Examples of pretargeting methods and applications
| Pretargeting agent | Target antigen | Chase | Radioactivity vector | Pretargeted radionuclides | Results | References |
|---|---|---|---|---|---|---|
| Murine antibody or ScFv-streptavidin conjugate | Ep-CAM | biotinylated galactosyl-human serum albumin | DOTA-biotin | Yttrium-90 | Clinical radioimmunotherapy of lung cancer and lymphoma | (Hnatowich et al. 1987; Houghton et al. 2017) |
| Pros: targeting efficacy, high tumour/non-tumour ratio | ||||||
| Cons: complexity (3 compounds), presence of endogenous biotin, toxicity (lung cancer), immunogenicity of streptavidin | ||||||
| Murine biotinylated antibody | CEA, tenascin | Avidin + streptavidin | DOTA-Biotin | Yttrium-90 | Clinical radioimmunotherapy of brain tumours | (Heskamp et al. 2017) |
| Pros: targeting efficacy, high tumour/non-tumour ratio | ||||||
| Cons: complexity (4 compounds), immunogenicity of avidin/streptavidin | ||||||
| Murine and chimeric bispecific antibody | CEA | None | Indium-EDTA haptens | Indium-111 | Clinical immunoscintigraphy | (Goldenberg 1997) |
| Pros: high tumour/non-tumour ratio, tumour imaging in the liver | ||||||
| Cons: low tumour uptake, moderate sensitivity | ||||||
| Murine and chimeric bispecific antibody (chemically conjugated Fab) | CEA | None | Bivalent haptens | Indium-111 | Clinical immunoscintigraphy, radioimmunotherapy | (Le Doussal et al. 1993; Lütje et al. 2015; McBride et al. 2009; Paganelli et al. 2001) |
| Iodine-131 | Pros: targeting efficacy, high tumour/non-tumour ratio, evidence of therapeutic effect in the clinic | |||||
| Cons: difficulties in the production of bispecific antibodies | ||||||
| Humanized bispecific antibody (Dock and Lock) | CEA, CD20, Trop2 | None | Bivalent haptens | Gallium-68 | Clinical immunoscintigraphy, radioimmunotherapy and immuno-PET, preclinical alpha-radioimmunotherapy | (Schoffelen et al. 2010; Schoffelen et al. 2013; Schoffelen et al. 2014; Sharkey et al. 2003; Sharkey et al. 2005) |
| Lutetium-177 | Pros: high tumour/non-tumour contrast ratio in PET imaging | |||||
| Bismuth-213 | Cons: Insufficient tumour irradiation for lutetium-177 therapy | |||||
| Murine antibody-oligonucleotide conjugate | Carcinoembryonic antigen | None | Complementary Morpholino oligonucleotide | Technetium-99 m | Preclinical targeting studies | (Halpern & Dillman 1987) |
| Pros: good tumour/non-tumour contrast ratio | ||||||
| Cons: preparation of antibody-oligonucleotide conjugates | ||||||
| Affibody-oligonucleotide conjugate | HER2 | None | DOTA-peptide nucleic acid | Indium-111 | Preclinical targeting and imaging studies | (Yao et al. 2004) |
| Pros: very good tumour/non-tumour contrast ratio | ||||||
| Cons: preparation of antibody-oligonucleotide conjugates | ||||||
| Humanized antibody-trans-cyclo-octene conjugate | TAG72, GPA33, CA19.9 | None or tetrazine-conjugated albumin attached to galactose or polystyrene beads | DOTA-PEG7-tetrazine | Indium-111, copper-64, lutetium-177, zirconium-89 | Preclinical targeting; immunoscintigraphy, PET imaging and dosimetry studies | (van Duijnhoven et al. 2015; van Essen et al. 2014; van Schaijk et al. 2005) |
| Pros: good tumour uptake and tumour/non-tumour contrast ratios, easy preparation of the reagents | ||||||
| Cons: need for a chase step to achieve excellent results | ||||||
| Diabody- or Affibody-trans-cyclo-octene conjugate | TAG72, HER2 | None | DOTA-PEG10-tetrazine | Lutetium-177 | Preclinical targeting and imaging studies | (Vugts et al. 2013; Yao et al. 1995) |
| Pros: good tumour uptake and tumour/non-tumour contrast ratios, easy preparation of the reagents, no need for a chase step | ||||||
| Cons: possible problem of kidney uptake for therapy |