In Vivo Head-to-Head Comparison of [18F]GTP1 with [18F]MK-6240 and [18F]PI-2620 in Alzheimer Disease

Emily Olafson; Matteo Tonietto; Gregory Klein; Edmond Teng; Andrew W. Stephens; David S. Russell; Karen Pickthorn; Sandra Sanabria Bohorquez

doi:10.2967/jnumed.124.268623

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FIGURE 1.
Average SUVR images from participants in cohort 1 (A), imaged with [¹⁸F]GTP1 and [¹⁸F]PI-2620, and cohort 2 (B), imaged with [¹⁸F]GTP1 and [¹⁸F]MK-6240, representing range of uptake in both cohorts. Each row contains average SUVR images from same participants.
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FIGURE 2.
Paired plots showing [¹⁸F]GTP1, [¹⁸F]PI-2620, and [¹⁸F]MK-6240 SUVR values in target cortical regions. Solid lines represent 1 participant. Dashed line indicates SUVR = 1. Cognitively unimpaired participant scanned with all 3 tracers is highlighted with darker black lines.
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FIGURE 3.
Association between [¹⁸F]GTP1 and [¹⁸F]PI-2620 SUVRs in target regions.
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FIGURE 4.
Association between [¹⁸F]GTP1 and [¹⁸F]MK-6240 SUVRs in target regions.
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FIGURE 5.
Paired plots showing [¹⁸F]GTP1, [¹⁸F]PI-2620, and [¹⁸F]MK-6240 SUVRs in off-target regions. Solid gray lines connect measurements from same participant. Dashed gray line is drawn at SUVR = 1.
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FIGURE 6.
Voxelwise SUVR analysis showing voxelwise t-statistics from voxelwise pairwise t-tests overlaid on Montreal Neurological Institute T1 template. Only significant pseudo t-scores (family wise error rate < 0.05) are displayed.
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FIGURE 7.
Association between [¹⁸F]GTP1 and [¹⁸F]PI-2620 (A) and [¹⁸F]GTP1 and [¹⁸F]MK-6240 in Braak II before (A and C) and after (B and D) regressing out signal from choroid plexus (CP). CU = cognitively unimpaired.

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TABLE 1.
Tracer Doses and Imaging Times
Tracer Target injected dose (MBq) Imaging window (min) Scan length (min)
[¹⁸F]GTP1 259 (±10%) 60–90 30
[¹⁸F]PI-2620 185 (±10%) 45–75 30
[¹⁸F]MK-6240 185 (±20%) 90–110 20

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TABLE 2.

Clinical and Demographic Characteristics of Two Cohorts

Parameter	Cohort 1: [¹⁸F]GTP vs. [¹⁸F]PI-2620					Cohort 2: [¹⁸F]GTP1 vs. [¹⁸F]MK-6240
Parameter	Whole cohort (n = 27)	CU (n = 5)	Prodromal AD (n = 10)	Mild AD (n = 10)	Moderate AD (n = 2)	Whole cohort (n = 22)	CU (n = 5)	Prodromal AD (n = 3)	Mild AD (n = 5)	Moderate AD (n = 9)
Sex (n)
Male	13	4	4	4	1	9	1	1	3	4
Female	14	1	6	6	1	13	4	2	2	5
Age (y)
Mean (SD)	70.2 (5.3)	71.2 (0.8)	71.7 (5.4)	69.9 (5.8)	61.5 (0.7)	71.3 (6.7)	68.0 (2.5)	73.7 (4.0)	72.7 (7.7)	71.0 (8.4)
Min–max	61–80	70–72	65–80	62–77	61–62	54–82	65–71	70–78	64–82	54–82
Race (n)
White	27	5	10	10	2	20	4	3	5	9
Ethnicity (n)
Hispanic/Latino	2	0	1	0	1	3	0	0	1	2
Not Hispanic/Latino	25	5	9	10	1	18	5	3	4	7
Not Stated						—	—	—	—	—
Centiloid, CTL
Mean (SD)	91.0 (41.1)	31.8 (40.4)	101.6 (34.1)	110.4 (19.2)	88.4 (33.7)	81.2 (52.3)	8.5 (23.5)	87.3 (26.6)	100.4 (20.7)	112.6 (40.7)
Min–max	−5.2–146.0	−5.2–81.1	46–146.0	77.1–140.7	64.6–112.3	−17.5–181.1	−17.5–106.1	56.8–106.1	68.6–119.1	63.2–181.1
Injected dose [¹⁸F]GTP1 (MBQ)
Mean (SD)	261 (11)	258 (4)	260 (14)	265 (7)	257 (26)	260 (8)	260 (6)	255 (6)	259 (2)	259 (7)
Min–Max	228–277	254–265	228–277	257–275	238–275	247–277	247–277	248–259	257–260	247–267
Injected dose^* (MBq)
Mean (SD)	189 (11)	193 (6)	187 (12)	187 (11)	197 (3)	190 (5)	192 (3)	193 (5)	187 (10)	190 (3)
Min–max	154–199	183–198	154–196	166–198	195–199	176–197	187–194	187–197	176–196	185–194
MMSE
Mean (SD)	25.5 (4.2)	30 (0)	26.9 (1.8)	23.8 (3.5)	16 (0)	21.8 (6.5)	29.8 (0.4)	27.6 (1.2)	20.8 (1.0)	15.9 (3.3)
Min–max	16–30	30-30	24–30	20–28	16–16	11–30	29–30	27–29	20–22	11–22
CDR-SB
Mean (SD)	0.5 (0.3)	0 (0)	0.5 (0)	0.7 (0.3)	0.75 (0.4)	0.6 (0.6)	0 (0)	0.5 (0)	0.6 (0.2)	0.9 (0.6)
Min–max	0–1	0–0	0.5–0.5	0.5–1	0.5–1	0–2	0–0	0.5–0.5	0.5–1	0.5–2

↵* Injected dose of [¹⁸F]PI-2620 in cohort 1 and [¹⁸F]MK-6240 in cohort 2.
CU = cognitively unimpaired; CTL = Centiloid; MMSE = Mini-Mental State Examination; CDR-SB = Clinical Dementia Rating Sum of Boxes.

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TABLE 3.

Cohort 1 ([¹⁸F]GTP1 and [¹⁸F]PI-2620) SUVR Quantification in Target Regions

ROI	[¹⁸F]GTP1 SUVR	[¹⁸F]PI-2620 SUVR	SUVR difference ([¹⁸F]GTP1 − [¹⁸F]PI-2620)	r² (95% CI)	Slope (95% CI)	Intercept (95% CI)
Braak I	1.61 ± 0.24	1.71 ± 0.29	−0.10 ± 0.16	0.71^* (0.50–0.84)	1.28 (1.03–1.73)	−0.35 (−1.10–0.03)
Braak II	1.32 ± 0.15	1.21 ± 0.17	0.11 ± 0.16^*	0.28^* (0.05–0.49)	1.14 (0.51–2.33)	−0.29 (−1.88–0.52)
Braak III	1.42 ± 0.23	1.47 ± 0.34	−0.05 ± 0.15	0.86^* (0.73–0.93)	1.51 (1.28–1.93)	−0.67 (−1.25 to −0.36)
Braak IV	1.61 ± 0.40	1.72 ± 0.51	−0.11 ± 0.18^*	0.91^* (0.80–0.96)	1.29 (1.15–1.59)	−0.36 (−0.80 to −0.16)
Braak V	1.25 ± 0.21	1.29 ± 0.27	−0.04 ± 0.12	0.82^* (0.64–0.91)	1.30 (1.06–1.68)	−0.34 (−0.77 to −0.06)
Braak VI	1.07 ± 0.13	1.10 ± 0.18	−0.03 ± 0.09	0.78^* (0.54–0.91)	1.46 (1.12–1.80)	−0.46 (−0.83 to −0.09)
Meta temporal	1.58 ± 0.35	1.74 ± 0.44	−0.16 ± 0.16^*	0.90^* (0.79–0.94)	1.29 (1.12–1.54)	−0.31 (−0.66 to −0.07)
Whole cortical gray	1.29 ± 0.23	1.39 ± 0.27	−0.10 ± 0.11^*	0.86^* (0.72–0.92)	1.23 (1.04–1.52)	−0.19 (−0.53–0.07)

↵* Indicates P (Bonferroni) < 0.05.
Slope of 2 indicates that for one-unit change in SUVR of [¹⁸F]GTP1, there is corresponding change in SUVR of 2 of [¹⁸F]PI-2620, on average.
Continuous data are median and range.

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TABLE 4.

Cohort 2 ([¹⁸F]GTP1 and [¹⁸F]MK-6240) SUVR Quantification in Target Regions

ROI	[¹⁸F]GTP1 SUVR	[¹⁸F]MK-6240 SUVR	SUVR difference ([¹⁸F]GTP1 – [¹⁸F]MK-6240)	r² (95% CI)	Slope (95% CI)	Intercept (95% CI)
Braak I	1.61 ± 0.41	1.97 ± 0.87	−0.36 ± 0.54	0.79^* (0.46–0.91)	2.32 (1.87–2.86)	−1.77 (−2.52 to −1.01)
Braak II	1.28 ± 0.20	1.32 ± 0.57	−0.04 ± 0.48	0.39^* (0.08–0.65)	4.32 (2.82–7.68)	−4.21 (−8.72 to −2.27)
Braak III	1.49 ± 0.38	1.99 ± 1.12	−0.50 ± 0.77^*	0.89^* (0.75–0.94)	3.07 (2.54–3.59)	−2.60 (−3.25 to −1.92)
Braak IV	1.63 ± 0.54	2.34 ± 1.39	−0.71 ± 0.89^*	0.90^* (0.80–0.94)	2.67 (2.21–3.28)	−2.02 (−2.83 to −1.41)
Braak V	1.28 ± 0.34	1.71 ± 1.02	−0.43 ± 0.73	0.82^* (0.66–0.89)	3.28 (2.40–4.64)	−2.49 (−4.01 to −1.49)
Braak VI	1.06 ± 0.15	1.23 ± 0.53	−0.17 ± 0.42	0.60^* (0.34–0.81)	4.46 (2.88–8.08)	−3.51 (−7.21 to −1.92)
Metatemporal	1.62 ± 0.49	2.31 ± 1.36	−0.69 ± 0.90^*	0.91^* (0.78–0.96)	2.85 (2.42–3.39)	−2.31 (−3.03 to −1.72)
Whole cortical gray	1.32 ± 0.33	1.78 ± 1.03	−0.46 ± 0.73	0.86^* (0.73–0.93)	3.35 (2.51–4.36)	−2.60 (−3.85 to −1.70)

↵* Indicates P (Bonferroni) < 0.05.
Slope of 2 indicates that for one-unit change in SUVR of [¹⁸F]GTP1, there is corresponding change in SUVR of 2 of [¹⁸F]MK-6240, on average.
Continuous data are median and range.

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TABLE 5.

Off-Target Signal Quantification (Mean ± SD)

ROI	[¹⁸F]GTP1 SUVR	[¹⁸F]PI-2620 SUVR	SUVR difference ([¹⁸F]GTP1 − [¹⁸F]PI-2620)	[¹⁸F]GTP1 SUVR	[¹⁸F]MK-6240 SUVR	SUVR difference [¹⁸F] (GTP1 − [¹⁸F]MK-6240)
Thalamus	1.07 ± 0.11	0.96 ± 0.12	0.10 ± 0.11^*	1.07 ± 0.10	0.75 ± 0.11	0.32 ± 0.15^*
Caudate	0.89 ± 0.13	0.80 ± 0.12	0.08 ± 0.12^*	0.97 ± 0.16	0.81 ± 0.26	0.16 ± 0.26
Putamen	1.25 ± 0.16	1.08 ± 0.15	0.18 ± 0.14^*	1.30 ± 0.17	1.06 ± 0.34	0.25 ± 0.32^*
Pallidum	1.21 ± 0.16	1.09 ± 0.20	0.12 ± 0.17^*	1.27 ± 0.20	0.95 ± 0.19	0.32 ± 0.23^*
Choroid plexus	1.13 ± 0.26	0.97 ± 0.17	0.16 ± 0.22^*	1.19 ± 0.28	0.79 ± 0.17	0.40 ± 0.25^*
Skull/meninges	1.17 ± 0.45	1.48 ± 0.39	−0.31 ± 0.27^*	1.12 ± 0.25	1.40 ± 0.41	−0.28 ± 0.38^*