Table 1.

I-124-AAVrh.10 and 9 vector positron emission tomography imaging in nonhuman primates

NHP No.a	Route	Vector Immune Status b	AAV Serotype/Transgene c	Day of Vector Administration	Labeled Activity, μCi	Injected Activity, μCi	Dose of Vector Administered, gc	Ratio of AAV dose to Injected Activity, gc/μCi	I-124 per Capsid	Detected Activity, μCid
1	Intravenous	Naive	10/mCherry	0	243	150	3.1 × 1012	2.1 × 1010	1.51	99
		Immune	10/FXN	63	1060	748	6.6 × 1012	0.9 × 1010	3.10	520
2	Intravenous	Naive	9/mCherry	0	110	59	5.7 × 1012	9.7 × 1010	0.37	40
		Immune	9/FXN	70	656	350	4.2 × 1012	1.2 × 1010	3.01	292
3	Intracisternal	Naive	10/mCherry	0	727	437	5.0 × 1012e	1.1 × 1010e	2.80e	351
		Immune	10/FXN	70	950	689	5.0 × 1012	0.7 × 1010	3.66	542
4	Intracisternal	Naive	9/mCherry	0	550	413	3.7 × 1012	0.9 × 1010	2.87	325
		Immune	9/FXN	91	420	278	1.1 × 1013	4.0 × 1010	0.74	258
5	Intracisternal	Naive	9/mCherryf	0	624	500	5.5 × 1013	1.1 × 1011	2.41	397
6	Intracisternal	NaI control	I-124-NaI	0	NA	410	—	—	—	281
	Intravenous	NaI control	I-124-NaI	112	NA	26	—	—	—	419

The initial I-124 calibrated activity for each experiment was 5.0 mCi, and the initial viral titer was ∼1 × 10¹³ gc. PET/CT was performed 1, 24, 48, and 72 h after I-124-labeled vector administration.

^aAll NHP (African green monkeys), adult males (5–7 years; 5.5–8.5 kg); total of n = 6 NHP were administered with n = 1/serotype/route plus n = 1 control for free I-124 activity. For NHP1–4, each was administered an I-124-labeled vector twice, with the second administration 63 to 91 days later; for NHP6 (NaI control), I-124-NaI was administered twice (different routes), with the second administered at 112 days.

^bNHP immunity status. For the initial vector administration, the NHP were immune-naive to the capsid; at the time of the second administration with the same capsid, the NHP had developed immunity against the capsid (Figs. 3A, B and 9A, B); the NaI control remained capsid immune-naive.

^cVectors tested were AAV9 (9) or AAVrh.10 (10) serotypes, with mCherry transgene for initial exposure, and human FXN transgene for the second immunized round of imaging.

^dActivity measured from the 1-h PET scan on day 0.

^eViral titer not performed for NHP3; the titer is an estimated value based upon the use of the same initial vector titer that was used for the other labeling experiments and resulting image quality.

^fNHP5 received a total vector dose ∼10 × higher (5.5 × 10¹³ gc, compared with ∼5 × 10¹² gc for NHP1–4). mCherry protein was assessed in this NHP at 6 weeks.

AAV, adeno-associated virus; CT, computed tomography; FXN, frataxin; I-124, iodine-124; NHP, nonhuman primates; PET, positron emission tomography.