Table 3.
Tissue concentrationsa (pM) of [125I]-IgG following intranasal or intra-arterial administration (high dose).
| Intranasal dose (2.5 mg) | Intra-arterial dose (6.5 μg) | |
|---|---|---|
| Blood | (pM) | (pM) |
| 0 min | 0 (4) | 4324.09 ± 73.67 (6) |
| 10 min | 486.91 ± 101.71 (4) | 3691.64 ± 280.2 (6) |
| 20 min | 1484.94 ± 323.69 (4) | 3322.45 ± 212.17 (6) |
| 30 min | 2663.77 ± 357.96 (4) | 2588.16 ± 158.35 (6) |
| Blood AUC (0–30 min) | (pM*min) | (pM*min) |
| 33,037.40 ± 5948.52 (4) | 99,209.03 ± 5937.43 (6) | |
| Nervous system regions | (pM) | (pM) |
| ACA & MCA b | 1510.13 ± 767.27 (5) d | 4.15 ± 1.49 (6) |
| Basilar & vertebral arteries c | 1581.38 ± 511.51 (5) d | 7.59 ± 3.20 (6) |
| Olfactory bulbs | 4418.54 ± 1862.50 (6) e | 2.53 ± 0.61 (6) |
| Frontal cortex | 547.44 ± 100.56 (6) e | 2.04 ± 0.33 (6) |
| Caudoputamen | 277.31 ± 63.95 (6) e | 2.39 ± 0.71 (6) |
| Motor cortex | 275.13 ± 48.4 (6) e | 1.62 ± 0.43 (6) |
| Primary somatosensory cortex | 226.06 ± 41.24 (5) e | 2.40 ± 0.41 (6) |
| Midbrain | 330.87 ± 69.00 (6) e | 1.70 ± 0.30 (6) |
| Posterior hippocampus | 276.28 ± 53.39 (6) e | 1.78 ± 0.41 (6) |
| Medulla | 424.54 ± 99.62 (6) e | 1.84 ± 0.43 (6) |
| Pons | 346.00 ± 51.44 (6) e | 2.11 ± 0.44(6) |
| Cerebellum | 249.73 ± 52.55 (6) e | 1.77 ± 0.37 (6) |
| Cervical spinal cord | 384.47 ± 68.31 (5) d | 2.43 ± 1.18(6) |
| Trigeminal nerves | 15,544.35 ± 5506.92 (6) e | 20.71 ± 3.81 (6) |
| Lymph nodes | (pM) | (pM) |
| Deep cervical lymph nodes | 1109.34 ± 341.06 (6) f | 255.99 ± 118.91 (6) |
| Superficial cervical lymph nodes | 53.97 ± 14.46 (6) | 2720.47 ± 353.65 (7) g |
| Axillary lymph nodes | 896.07 ± 399.82 (6) g | 38.89 ± 11.18 (6) |
Blood, nervous system, and lymph node radiolabel concentrations following intranasal or intra-arterial administration of [125I]-IgG (high doses). Intranasal administration of a high (50-fold higher than tracer) dose (2.5 mg) was performed drop wise (4 drops of 12 μl each) over approximately 15 min. Intra-arterial administration of a dose (6.5 μg) that resulted in similar end point blood concentrations as the intranasal dose was performed as a bolus dose (500 μl) over 1–2 min. The concentration at time zero following intra-arterial administration of [125I]-IgG was estimated by extrapolation.
Data are presented as mean ± S.E.M. (n independent experiments);
anterior cerebral and middle cerebral arteries – isolated perfused vessels (indirect measure of perivascular compartment);
isolated perfused posterior circulation vessels mainly comprising the basilar and vertebral arteries (a small portion of the proximal posterior cerebral and superior cerebellar arteries are also included; indirect measure of perivascular compartment); Statistical analysis for tissue samples - intranasal vs intra-arterial dosing: Two-tailed Studenťs t-test –
Mann-Whitney U = 0, p = .004;
Mann-Whitney U = 0, p = .002;
t(10) = 2.363, p = .04. Mann-Whitney Rank sum test –
Mann-Whitney U = 0, p = .001.