Table 1. Biodistribution of TPP1 preparations 24 hours following IV administration.
| Genotype | Tpp1(+/+) | Tpp1(−/−) | ||||
| Preparation | - | Unmodified TPP1 | OX-TPP1 | DG-TPP1 | ||
| Dose (mg) | - | 0.12 | 2.0 | 0.12* | 2.0* | 0.12 |
| Sample size | 5 | 5 | 8 | 2 | 3 | 2 |
| TPP1 specific activity, pmol/organ (% of wild-type) | ||||||
| Brain | 52.6±17.4 (100%) | 1.4±0.4 (3%) | 5.4±2.9 (10%) | 0.3±0.4 (1%) | 2.7±1.4 (5%) | 0.7±0.1 (1%) |
| Liver | 995±238 (100%) | 1182±384 (119%) | 13416±2811 (1348%) | 361.8±56.3 (36%) | 5357±802 (538%) | 778.7±13 (78%) |
| Spleen | 38.7±20.0 (100%) | 43.9±45.4 (113%) | 393.6±175.5 (1017%) | 3.1±1.4 (8%) | 108±22.6 (279%) | 19.7±1.6 (51%) |
| Kidney | 215±58.8 (100%) | 17.4±14.5 (8%) | 102±20.4 (47%) | 7.0±3.2 (3%) | 96.8±21.9 (45%) | 10.1±1.9 (5%) |
| Heart | 8.4±3.5 (100%) | 3.1±2.8 (37%) | 59.4±27.3 (707%) | 2.7±0.6 (32%) | 68.6±52.8 (817%) | 1.2±0.3 (14%) |
| Lung | 29.3±11.0 (100%) | 5.7±6.6 (19%) | 43.2±23 (147%) | 3.1±3.1 (11%) | 53±19.9 (181%) | 1.5±1.4 (5%) |
| Sum of tissues {% injected} | 1339 | 1253{62%} | 14020{42%} | 378{23%} * | 5686{21%} * | 812{40%} |
*
Only 82% of the oxidized proTPP1 could be autocatalytically converted to active enzyme. The dose represents total proenzyme based on concentration as determined by absorbance measurements, while % of injected activity recovered from all tissues analyzed is corrected for the amount of active enzyme (e.g., for OX-TPP1, pmol total injected*0.82).
Data are expressed as pmol TPP1 per organ and also compared to levels present in control Tpp1(+/+) mice. Note that for total recovery, the sum of the TPP1 detected in all tissues analyzed 24 hours after administration is compared to the administered dose without correcting for half-life. Data normalized to protein are presented in Table S1.