Contrast Media & Molecular Imaging

Review Article

Pretargeted Nuclear Imaging and Radioimmunotherapy Based on the Inverse Electron-Demand Diels–Alder Reaction and Key Factors in the Pretargeted Synthetic Design

Table 1

Overview of reported pretargeted nuclear imaging and radioimmunotherapy studies based on the IEDDA click chemistry.


Author (year)	Xenograft model	Target	Immunoconjugate	Tz radioligand	Others

Rossin et al. (2010) [13]	LS174T colon cancer	TAG-72	CC49-PEG₁₂-benzamide-TCO	¹¹¹In-DOTA-PEG₁₁-bispyridyl Tz	—
Rossin et al. (2013) [14]	LS174T colon cancer	TAG-72	CC49-benzamide-TCO or CC49-PEG₁₂-benzamide-TCO	¹¹¹In-DOTA-PEG₁₁-bispyridyl Tz	Axially substituted TCO with bulky linker and no PEG linker compared with Reference [7]
Rossin et al. (2013) [15]	LS174T colon cancer	TAG-72	CC49-benzamide-TCO	¹¹¹In-DOTA-PEG₁₁-bispyridyl Tz	Clearing agent and no PEG linker compared with Reference [7]
Rossin et al. (2014) [16]	LS174T colon cancer	TAG-72	CC49-acetamide-TCO	¹¹¹In-DOTA-PEG₁₁-bispyridyl Tz	Acetamide linker between CC49 and TCO compared with benzamide linker in Reference [7–9]
Altai et al. (2016) [20]	SKOV-3 ovarian cancer	HER2	Z₂₃₉₅ (affibody)-PEG₄-TCO	¹¹¹In-DOTA-PEG₁₀-bispyridyl Tz	—
van Duijnhoven et al. (2015) [21]	LS174T colon cancer	TAG-72	AVP04-07 (diabody)-benzamide-TCO	¹¹¹In-DOTA-PEG₁₁-bispyridyl Tz	—
García et al. (2016) [23]	LS174T colon cancer	TAG-72	CC49-TCO	^99mTc-HYNIC-Tz	—
García et al. (2018) [24]	B16-F10 melanoma	VEGF	Bevacizumab-TCO	^99mTc-HYNIC-PEG4-Tz^99mTc-HYNIC-PEG₅-polypeptide-Tz	Polypeptide: Gly-Arg-Glu-Arg-Glu-Lys
Yazdani et al. (2016) [25]	—	Bone	BP (bisphosphonate)-TCO	^99mTc-Tz complex	—
Zeglis et al. (2013) [26]	SW1222 colorectal cancer	HuA33	A33-TCO	⁶⁴Cu-NOTA-Tz	—
Zeglis et al. (2015) [27]	SW1222 colorectal cancer	HuA33	A33-TCO	⁶⁴Cu-NOTA-PEG₇-Tz⁶⁴Cu-SarAr-Tz	⁶⁴Cu-SarAr-Tz net charge (+2)
Evans et al. (2014) [28]	A431 cutaneous squamous cancer	EGFR	Cetuximab-PEG₄-TCO	⁶⁸Ga-DOTA-Tz	—
Nichols et al. (2014) [5]	LS174 T colon cancer	HuA33	A33-TCO	⁶⁸Ga-DTPA aminodextran Tz-coated polymer	Aminodextran polymer: 16 kDa
Devaraj et al. (2012) [29]	LS174 T colon cancer	HuA33	A33-TCO	¹⁸F aminodextran Tz-coated polymer (¹⁸F-PMT10 and PMT40)	Aminodextran polymer: 10 and 40 kDa
Meyer et al. (2016) [34]	BxPC3 pancreatic cancer	CA19.9	5B1-TCO	Al[¹⁸F]-NOTA-PEG₁₁-Tz	—
Shi et al. (2018) [35]	HCT116 colon cancer	EGFR	Cetuximab-Tz and panitumumab-Tz	Al[¹⁸F]-NOTA-TD (a Reppe anhydride derivative)	An inverse strategy and replaced TCO with a Reppe anhydride derivative
Denk et al. (2016) [36]	—	Lung	MSNs-TCO and MSNs-s-TCO	¹¹C-Tz	First¹¹C-labeled Tz
Keinänen et al. (2017) [37]	—	Spleen and liver	NPs-TCO	¹⁸F-Tz	—
Keinänen et al. (2017) [38]	A431 epidermoid carcinoma BT-474 ductal carcinoma	EGFR HER2	Cetuximab-TCO and trastuzumab-TCO	¹⁸F-Tz	—
Houghton et al. (2017) [39]	BxPC3 pancreatic cancer	CA19.9	5B1-TCO	¹⁷⁷Lu-DOTA-PEG₇-Tz¹⁷⁷Lu-CHX-A”-DTPA-PEG₇-Tz	—
Membreno et al. (2018) [40]	SW1222 colorectal cancer	HuA33	A33-TCO	¹⁷⁷Lu-DOTA-PEG₇-Tz	—
Shah et al. (2017) [41]	LS174 T colon cancer	TAG-72	CC49-TCO	²¹²Pb-DOTA-PEG₁₁-bispyridyl Tz	—