Table 2.

Comparison of radiometal RIT mAb formats developed for targeting EGFR

mAb	mAb Format	Radionuclide	Chelator	Dose Administered*	Study Highlights	Cancer cell line/xenograft
Panitumumab	Full-length	212Pb	TCMC	0.37-1.48 MBq	MS for 0.37 MBq and 0.74 MBq cohorts were 39 d and 58 d compared to 15 d for control untreated mice.	LS-174T i.p. xenografts 101
		177Lu	DOTA-AuNP†	1.5-4.5 MBq	A dose dependent decrease in in vitro clonogenic survival studies was observed.	MDA-MB-468 and MDA-MB-231 104
			DOTA	14.8 MBq	Tumor growth was inhibited up to 36 d p.i. compared to PBS and non-labeled control; no significant adverse events for body weight nor mortality noted.	UM-SCC-22B 105
			DOTA-MCP‡	6 MBq	A 6 MBq dosed activity in non-tumor bearing mice did not cause significant decreases in RBC, WBC or platelets, no increase in serum ALT and only a small increase in Cr. [177Lu]Lu-MCP-panitumumab administered mice exhibited significantly decreased tumor volumes at 33 d p.i. compared to control.	PANC-1 107
	F(ab)'2	212Pb	TCMC	0.37-3.7 MBq i.p. 0.185-1.85 MBq	1.11 MBq (i.p.) and 0.74 MBq (i.v.) were selected as effective therapeutic doses with MS of 289 d and 46 d, respectively. Although benefit of i.p. was noted, i.v. administration was chosen for co-administration with gemcitabine (MS: 208 d) or paclitaxel (MS: 239 d).	LS-174T i.p. 119
		64Cu	NOTA	1.85-9.25 MBq	3.7 MBq administered every two weeks was selected. No generalized toxicity of the tracer was noted.	OCIP23 pancreatic PDX and PANC-1 120
Cetuximab	Full-length	177Lu	DOTA	14.8 MBq	A significant tumor growth delay was observed up to 30 d p.i., but tumors grew significantly larger (>1500 mm3 35 d p.i.) compared to [177Lu]Lu-DOTA-panitumumab; no significant adverse events for body weight nor mortality noted.	UM-SCC-22B 105
			PCTA	12.95 MBq	A significant difference in tumor volume 16 d p.i. was observed compared to saline or non-labeled cetuximab controls.	TE-8 109
				12.95 MBq	A 55% reduction in tumor volume after treatment was observed. There was a significant decrease in final tumor volume 30 d p.i. compared to saline and non-labeled cetuximab controls.	SNU-1066 111
		188Re	N/A	22.2-59.2 MBq	MTD was determined to be 37 MBq. Treatment studies were conducted with 29.6 and 22.2 MBq with MS of 62.5 and 61.75 d (control MS: 36.75 d).	NCI-H292 108
		64Cu	PCTA	11.1-74 MBq	MTD: 22.2 MBq. Survival of mice was at 40% when treated with adjuvant [64Cu]Cu-PCTA-cetuximab at 83 d with no detectable lesions.	x-PA-1-DC orthotopic xenograft 110
		212Pb	TCMB	0.37-1.48 MBq	0.37 MBq was chosen as the effective therapeutic dose due to lack of toxicity and a MS that lasted beyond 294 d.	LS-174T i.p. xenografts 113
	F(ab)'2	177Lu	DOTAGA	2-8 MBq	Colorectal tumor growth was inhibited for mice administered 4 and 8 MBq compared to 2 MBq and control. Acute weight loss was observed at the 4 MBq dose 20 d p.i. and mice recovered by 23 d p.i.	A431 112

^†AuNP: Gold nanoparticles used for radiosensitization;

^‡MCP: Metal chelating polymers;

*All activities administered i.v. unless otherwise noted.

Abbreviations: TCMC, 1,4,7,10-tetraza-1,4,7,10-tetra(2-carbamoylmethyl)cyclododecane; MS, median survival; RBC, red blood cells; WBC, white blood cells; ALT, alanine aminotransferase; Cr, creatinine; MTD, maximum tolerated dose; PCTA, 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triacetic acid.