Table 3.
Amyloid pathology score by immunohistochemistry using the 4G8 antibody, imaging agent used (ET3-73 targeted or control untargeted) and individual measures of nanoparticle presence in mouse brain. Semi-quantitative scoring of Aβ plaques is by a fourtier scale of 0 (none), 1 (sparse), 2 (moderate), and 3 (severe/frequent). Presence of positive signal for ICG, ligand, and MRI is denoted by an X, absence by a -. There is a 100% correlation between the immunohistochemistry results and each of the measures of nanoparticle presence. APP+ mice of either strain (TetO/APPswe (*), or Tg2576 (#) treated with the targeted agent showed positive signal in MRI, immunohistochemistry and fluorescent markers of nanoparticle presence, while APP+ mice of either strain treated with untargeted agent showed no signal, and APP− mice showed no signal regardless of treatment. Data is consistent with the targeted agent being able to access amyloid plaques and bind to them, while being cleared in the absence of binding, and no binding occurring in the absence of the targeting ligand. McNemar’s exact test for correlated populations obviously yields p=0 because of the 100% concordance between the immunohistochemistry and MRI results. Cohen’s Kappa yields κ=1 confirming the strong correlation. The standard error of κ is calculated as 0.224, thus yielding a z of 4.47 for the correlation between the two modalities. Correspondingly, p:H0 testing the null hypothesis that the two modalities are independent yields p=3.87×10−6, strongly supporting the equivalence of the two modalities. The sample size at which a 100% concordant set of tests yields p<0.01 is 3, confirming that the current sample size is adequate to support the test of this hypothesis.
| APP+ Genotype | Treatment | Pathology | ICG | Ligand | MRI |
|---|---|---|---|---|---|
| Positive* | Targeted | 3 | X | X | X |
| Positive# | Targeted | 1 | X | X | X |
| Positive# | Targeted | 1 | X | X | X |
| Positive# | Targeted | 0 | - | - | - |
| Positive# | Targeted | 0 | - | - | - |
| Positive# | Targeted | 0 | - | - | - |
| Positive* | Targeted | 3 | X | X | X |
| Positive* | Targeted | 3 | X | X | X |
| Positive* | Targeted | 3 | X | X | X |
| Positive* | Targeted | 3 | X | X | X |
| Positive* | Targeted | 3 | X | X | X |
| Negative* | Targeted | 0 | - | - | - |
| Negative* | Targeted | 0 | - | - | - |
| Negative# | Targeted | 0 | - | - | - |
| Negative# | Targeted | 0 | - | - | - |
| Negative# | Targeted | 0 | - | - | - |
| Negative# | Targeted | 0 | - | - | - |
| Positive# | Untargeted | 0 | - | - | - |
| Positive# | Untargeted | 0 | - | - | - |
| Negative# | Untargeted | 0 | - | - | - |