Different toxicity profiles for drug- versus radionuclide-conjugated BR96 monoclonal antibodies in a syngeneic rat colon carcinoma model

Figures & data

Table I. Toxicity.

		Number of rats
Adverse event	Treatment	Grade 1 toxicity^1(mild)	Grade 2 toxicity (moderate)	Grade 3 toxicity (severe)
Weight	600 MBq/kg ^177Lu-BR96	6	0	0
	15 mg/kg b-BR96-MMAF	0	1	5
	15 mg/kg BR96	0	0	0
ALAT	600 MBq/kg ^177Lu-BR96	5	0	0
	15 mg/kg b-BR96-MMAF	0	5	1
	15 mg/kg BR96	1	0	0
ASAT	600 MBq/kg ^177Lu-BR96	4	2	0
	15 mg/kg b-BR96-MMAF	0	0	6
	15 mg/kg BR96	0	1	0
ALP	600 MBq/kg ^177Lu-BR96	2	4	0
	15 mg/kg b-BR96-MMAF	2	1	3
	15 mg/kg BR96	0	0	0
G-GT	600 MBq/kg ^177Lu-BR96	0	2	0
	15 mg/kg b-BR96-MMAF	0	2	4
	15 mg/kg BR96	0	0	0
Bilirubin	600 MBq/kg ^177Lu-BR96	0	0	0
	15 mg/kg b-BR96-MMAF	0	0	0
	15 mg/kg BR96	0	0	0
Creatinine	600 MBq/kg ^177Lu-BR96	6^2	0	0
	15 mg/kg b-BR96-MMAF	6	0	0
	15 mg/kg BR96	5	0	0

¹NCI Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE). The WBC, PLT, and RBC are not included as the CTCAE definitions of grades for these parameters cannot be easily applied to rat data.

²3/6 rats had grade 1 toxicity prior to administration of the conjugate.

Figure 1. Survival of animals given b-BR96-MMAFconjugates (group 1), ¹⁷⁷Lu-labeled BR96 (group 2), and unconjugated BR96 (group 3) monitored for 100 days. Deaths before day 21 were attributed to toxicity. All the late deaths (after day 45) were attributed to metastatic disease. Four of the six animals treated with unconjugated BR96 (group 3) died due to local recurrences and the other two due to distant metastases. No animal treated with conjugated BR 96 (group 1&2) had a local recurrence. At termination of the study (day 100), two rats in group 1, and four rats in group 2 were still alive. In one rat in group 2, metastatic disease was detected.

Figure 2. Normalized body weights of animals given b-BR96-MMAFconjugates (group 1), ¹⁷⁷Lu-labeled BR96 (group 2), and unconjugated BR96 (group 3).

Figure 3. Numbers of leukocytes (A) and platelets (B) in animals given b-BR96-MMAF conjugates (group 1), ¹⁷⁷Lu-labeled BR96 (group 2), and unconjugated BR96 (group 3).

Figure 4. Serum levels of ASAT (A) and ALAT (B) in animals given b-BR96-MMAFconjugates (group 1), ¹⁷⁷Lu-labeled BR96 (group 2), and unconjugated BR96 (group 3).