Minor changes in effective half-life during fractionated ¹⁷⁷Lu-Octreotate therapy

Figures & data

Table I. Absorbed dose for left and right kidney in early and late therapy for all 30 patients receiving 7.4 GBq. The late dose is also presented with the kinetics from therapy 1 (D₁₄).

	D1 [Gy]		D4 [Gy]		D14 [Gy]
Patient number	Kidney Right	Kidney Left	Kidney Right	Kidney Left	Kidney Right	Kidney Left
1	2.9	2.3	3.7	2.9	3.2	2.2
2	3.6	3.3	4.5	4.4	5.0	4.3
3	3.0	3.0	3.4	3.2	4.0	3.8
4	3.9	3.1	3.9	4.7	4.3	3.4
5	4.7	4.6	3.8	3.9	4.0	4.1
6	3.7	3.3	4.4	3.9	4.5	4.0
7	5.1	4.9	5.9	5.8	6.3	5.8
8	3.8	3.0	5.0	3.9	6.7	5.0
9	4.6	4.1	3.8	3.7	4.4	3.6
10	4.0	4.0	3.9	3.7	4.1	3.7
11	3.8	4.0	3.0	3.0	2.8	3.2
12	3.5	4.2	4.3	4.5	5.4	5.1
13	3.1	2.7	2.9	2.8	2.9	2.9
14	3.5	3.0	3.4	4.0	3.6	3.9
15	2.2	2.0	2.5	2.2	2.3	1.9
16	4.6	4.9	6.8	7.0	8.5	8.8
17	4.8	4.7	4.8	4.6	5.4	5.3
18	2.3	1.7	3.1	2.9	4.2	3.4
19	3.8	3.1	4.7	4.1	5.4	4.7
20	4.9	4.0	5.1	5.0	5.4	4.8
21	3.3	2.6	4.4	4.0	6.8	4.2
22	4.0	3.7	4.8	4.7	4.8	4.9
23	3.2	3.0	4.9	5.6	5.7	5.4
24	3.1	3.3	4.8	4.7	6.2	5.0
25	4.1	3.6	4.5	4.0	4.4	4.2
26	6.3	6.4	6.8	6.9	6.8	7.0
27	4.3	4.5	3.9	3.5	3.9	3.5
28	4.0	3.7	6.0	6.0	6.3	6.0
29	4.6	4.0	4.9	4.4	5.0	4.8
30	2.9	2.7	5.1	4.9	5.5	4.5

Figure 1. Dotplot of the ratios of the effective half-life between cycle 4 or 5 to cycle 1.

Table II. The statistics of the ratios of the effective half-life of the solid organs at risk in cycle 4 or 5 versus cycle 1.

Variable	Organ	N	P	1st quartile	median	3rd quartile	mean
Effective half-life	Kidney Right	30	0.014	0.89	0.97	1.01	0.95
Ratio (Rteff)	Kidney Left	30	0.869	0.93	1.01	1.05	1.00
	Liver	30	0.188	0.77	0.96	1.05	0.96
	Spleen	26	0.879	0.94	1.02	1.06	1.01
	Tumor	30	0.017	0.82	0.89	1.05	0.93
Activity concentration	Kidney Right	30	0.001	1.00	1.14	1.32	1.17
Ratio (Ruptake)	Kidney Left	30	0.001	1.07	1.21	1.40	1.24
	Liver	30	0.026	0.52	0.82	1.09	0.83
	Spleen	26	0.128	0.91	1.08	1.45	1.21
	Tumor	30	0.000	0.42	0.62	0.80	0.61
Absorbed dose	Kidney Right	30	0.001	1.02	1.14	1.42	1.24
Ratio (Rdose)	Kidney Left	30	0.002	1.06	1.17	1.45	1.24
	Liver	30	0.008	0.61	0.82	1.03	0.89
	Spleen	26	0.099	0.86	1.15	1.41	1.19
	Tumor	30	0.000	0.49	0.67	0.83	0.64

Figure 2. Comparison of the effective half-life changes in the left and right kidney during therapy.

Figure 3. Example of change in tumor volume (liver metastases, hair cross on caudal pole of right kidney) during therapy in patient no. 8 (rectal carcinoid). SPECT/CT images 24 h after cycle 1 (a, b) and 6 (c, d); (a, c: fused sagittal views) b, d: maximum intensity projections.

Table III. Effective half-life (t_eff) and uptake values for left and right kidney in early and late therapy cycles.

	teff 1 [h]		C24 1 [MBq/ml]		teff 4 [h]		C24 4 [MBq/ml]
Patient number	Kidney Right	Kidney Left	Kidney Right	Kidney Left	Kidney Right	Kidney Left	Kidney Right	Kidney Left
1	53.6	44.2	0.35	0.29	64.8	56.8	0.37	0.30
2	55.9	53.2	0.40	0.38	54.4	57.1	0.53	0.49
3	55.5	59.6	0.36	0.32	47.5	51.8	0.40	0.36
4	76.7	60.8	0.34	0.32	68.3	68.6	0.36	0.36
5	44.7	44.5	0.62	0.62	44.2	45.0	0.51	0.53
6	44.6	43.4	0.50	0.46	45.6	45.3	0.61	0.55
7	51.3	50.4	0.59	0.57	50.0	51.7	0.75	0.71
8	70.6	62.7	0.35	0.31	50.4	49.8	0.54	0.46
9	55.5	52.7	0.52	0.49	55.1	53.2	0.48	0.41
10	50.2	46.5	0.48	0.49	50.2	46.9	0.49	0.47
11	56.7	60.9	0.44	0.43	58.8	56.5	0.32	0.34
12	67.8	66.0	0.34	0.39	54.1	57.5	0.48	0.47
13	53.3	54.0	0.35	0.30	53.3	55.9	0.33	0.33
14	53.3	45.5	0.40	0.39	50.3	47.4	0.50	0.65
15	47.2	43.1	0.35	0.34	58.4	55.3	0.27	0.25
16	59.5	60.2	0.48	0.50	47.5	49.0	0.83	0.85
17	47.9	48.7	0.59	0.57	44.1	43.7	0.64	0.61
18	76.0	62.7	0.20	0.16	58.7	55.6	0.34	0.32
19	54.8	49.1	0.43	0.40	50.2	44.2	0.59	0.54
20	57.6	53.2	0.57	0.51	56.2	56.3	0.57	0.55
21	66.1	48.0	0.31	0.31	46.7	48.1	0.59	0.50
22	44.7	44.4	0.55	0.52	45.2	44.2	0.63	0.64
23	59.5	49.1	0.35	0.37	53.0	52.4	0.60	0.69
24	50.8	44.1	0.40	0.43	43.5	44.9	0.68	0.64
25	51.0	50.4	0.48	0.44	53.3	49.0	0.53	0.50
26	52.0	53.4	0.75	0.75	53.2	53.9	0.78	0.79
27	46.7	46.8	0.58	0.62	48.3	49.1	0.48	0.43
28	48.7	44.7	0.51	0.52	48.3	47.1	0.70	0.73
29	58.0	54.2	0.49	0.45	55.1	50.9	0.52	0.52
30	57.9	48.5	0.31	0.33	55.9	49.9	0.57	0.54
mean	55.6	51.5	0.446	0.433	52.2	51.2	0.534	0.518
1st quartile	50.3	45.7	0.352	0.330	47.7	47.2	0.480	0.416
Median	54.2	49.8	0.435	0.433	51.7	50.4	0.530	0.511
3rd quartile	58.0	54.2	0.516	0.510	55.1	55.6	0.609	0.634

Table IV. Changes in tumor size according to RECIST and changes in tumor and liver volume: Columns 1 and 2: Difference in percent between tumor sizes at first and second complete dosimetry, and between first dosimetry and at time of best response according to RECIST criteria. Columns 3 to 6: changes in tumor and liver volumes, respectively according to simplified volume calculation model (tumors represented by spheres, summed tumor volume of all evaluable tumors according to CT; liver volume represented by an ellipsoid). Patients with abundant tumor in the liver occasionally showed initially a more marked decrease in liver volume than in tumor volume (patients 1 and 8), patient 4 showed an increase of liver volume after the first treatments, that preceded a significant volume reduction of liver metastases, and subsequent volume reduction of the liver later on during therapy. Remodeling of the liver and inflammatory reaction being potential reasons. Patient 19 underwent hemihepatectomy including resection of remnants of large liver metastasis during therapy.

	Tumor				Liver
Patient number	RECIST at dosimetry [%]	RECIST at best [%]	Δ Volume at dosimetry [ml]	Δ Volume at best [ml]	Δ Volume at dosimetry [ml]	Δ Volume at best [ml]
1	−9.5	−23	−483	−635	−848	−646
2	−19.5	−39	−331	−504	451	491
3	−41	−89	−1466	−2012	n.a.	n.a.
4	1	−50	−172	−1432	848	−1374
5	−10	−39	−8	−25	−5	−250
6	−27.5	−39	−42	−53	−316	−360
7	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.
8	−32	−53	−1589	−2032	−1329	−1281
9	−0	n.a.	−25	n.a.	n.a.	n.a.
10	−35	−38	−25	−26	−13	85
11	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.
12	−43	n.a.	−298	n.a.	n.a.	n.a.
13	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.
14	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.
15	−30	−38	−226	−256	−162	−222
16	6	−25	16	−39	56	−290
17	−38	n.a.	−10	n.a.	−14	n.a.
18	−25	−62	−98	−152	−213	−358
19	−22	−40	−214	−333	−227	−1134
20	−27	−27	−128	−128	−806	−806
21	−14	−55	−400	−922	−425	−996
22	−17	−17	−137	−137	−424	−424
23	−12	−17	−801	−1023	−421	n.a.
24	−10	−44	−1038	−1107	−1417	−1106
25	−12	−17	−202	−268	172	−565
26	−82	−86	−34	−36	151	107
27	−16	−24	−50	−73	n.a.	n.a.
28	−20	n.a.	−26	n.a.	−110	n.a.
29	−29	−37	−327	−380	n.a.	n.a.
30	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.

Figure 4. Dotplot of the ratios of the activity concentration after 24 h between cycle 4 or 5 to cycle 1.

Figure 5. Dotplot of the ratios of the absorbed dose between cycle 4 or 5 to cycle 1.

Figure 6. First row: dorsal view derived from 24 h whole body scan, cycle 1 to 6 in patient no. 8 (rectal carcinoid). Note the side difference between kidney uptake during therapy (arrow on caudal pole of right kidney at first cycle). Second row: Cystatin-C derived GFR (mL/min/1.73 m², normal range > 80 (age adjusted) and P-creatinine (μmol/l) at corresponding times.