Anti-CD45 Monoclonal Antibody YAML568: A Promising Radioimmunoconjugate for Targeted Therapy of Acute Leukemia

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FIGURE 1.
Clearance of ¹¹¹In-labeled YAML568 from blood is shown for 2 patients, with (patient 5) and without (patient 1) prior administration of unlabeled antibody (Table 1).
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FIGURE 2.
Biodistribution of ¹¹¹In-labeled YAML568 (left, mirrored anterior view; right, posterior view) is shown for 2 patients, with (A, patient 5) and without (B, patient 1) prior administration of unlabeled antibody (Table 1).
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FIGURE 3.
Pharmacokinetic data for ¹¹¹In-labeled YAML568 are shown for 2 patients, with (A, patient 5) and without (B, patient 1) prior administration of unlabeled antibody (Table 1). Measurements without preloading were terminated after 2 d because biodistribution was unfavorable for therapy.

TABLE 1

Patient Data

				Unlabeled Ab		Red marrow leukemic blast infiltration (%)	Peripheral blood leukemic blast counts/μL
Patient no.	Disease	Age (y)	Sex	mg	mg/kg	Red marrow leukemic blast infiltration (%)	Peripheral blood leukemic blast counts/μL
1	AML, refractory	61	F	0	0.00	80	0
2	AML, relapsing	56	M	10	0.16	80	8,800
3	ALL, refractory	48	M	10	0.14	20	0
4	AML, relapsing	54	F	30	0.48	50	100
5	AML, refractory	44	M	45	0.49	50	800
6	AML, refractory	58	M	47	0.51	20	0
7	AML, refractory	53	M	42.5	0.48	90	100
8	AML, relapsing	49	M	43	0.51	80	800
Mean ± SD	—	53 ± 6	—	—	—	59 ± 28	1,325 ± 3,040

TABLE 3

Estimated Radiation-Absorbed Dose per Injected Activity (mGy/MBq) and Therapeutic Ratio of Red Marrow to Liver for ⁹⁰Y-Labeled YAML568 Antibody

Patient no.	Red marrow	Spleen	Liver	Kidneys	Lungs	Total body	Red marrow/liver
1	2.0	31	5.5	1.0	0.1	0.6	0.4
2	3.6	29	6.8	0.5	0.1	0.5	0.5
3	2.5	35	6.7	0.4	0.1	0.5	0.4
4	6.4	19	6.0	1.4	0.1	0.7	1.1
5	8.2	12	4.6	1.2	0.1	0.6	1.8
6	5.1	26	2.7	0.5	0.2	0.5	1.9
7	5.6	21	3.4	1.3	0.2	0.6	1.6
8	6.8	18	2.8	1.3	0.2	0.5	2.4
Mean ± SD^*	5.0 ± 2.2	24 ± 8	4.8 ± 1.7	0.9 ± 0.4	0.1 ± 0.1	0.6 ± 0.1	1.3 ± 0.8
Mean ± SD^†	6.4 ± 1.2	19 ± 5	3.9 ± 1.4	1.1 ± 0.4	0.1 ± 0.1	0.6 ± 0.1	1.8 ± 0.5

	Unlabeled antibody (mg/kg body weight)
Organ	y-intercept	Slope	P	R²
Red marrow	1.8 ± 0.7	9.2 ± 1.9	0.003	0.80
Spleen	34 ± 3	−29 ± 9	0.017	0.64
Liver	6.8 ± 0.9	−5.6 ± 2.4	0.054	0.49