Article Figures & Data
Figures
- FIGURE 1.
Structures of small-molecule inhibitors of PSMA, 99mTc-MIP-1404 and 99mTc-MIP-1405.
- FIGURE 2.
Blood clearance and urinary excretion of 99mTc-MIP-1404 and 99mTc-MIP-1405 in healthy subjects (A and B) and in patients with PCa (C and D).
- FIGURE 3.
Whole-body planar images of 99mTc-MIP-1404 (A) and 99mTc-MIP-1405 (B) at different times after intravenous injection showing biodistribution in patient with metastatic PCa.
- FIGURE 4.
Differences in urinary excretion between 99mTc-MIP-1404 and 99mTc-MIP-1405. The planar and SPECT images of 99mTc-MIP-1404 (A and B) show minimal urinary excretion and bladder (BL) activity, compared with that of 99mTc-MIP-1405 (C and D). Images also identify metastasis in lymph node (LN) in pelvis and paraaortic lymph nodes (PLN).
- FIGURE 5.
Tumor uptake of 99mTc-MIP-1404 (A) or 99mTc-MIP-1405 (B) at 4 h in patient with metastatic PCa, compared with that of standard bone scan (C). Images also show uptake of radiotracer in normal parotid and salivary glands. Ant = anterior; Post = posterior.
- FIGURE 6.
Comparison of 99mTc-MIP-1404 scan with bone scans in patient with metastatic PCa. PSMA imaging with 99mTc-MIP-1404 (in March) detected more metastatic lesions than 2 bone scans obtained either before (in January) or after (in June) PSMA scan. Ant = anterior; Post = posterior. Metastatic sites (red arrows) shown in PSMA scan (B) were detected by bone scan (C) performed 3 mo after PSMA scan.
- FIGURE 7.
T/B ratios of 99mTc-MIP-1404 and 99mTc-MIP-1405 in patients with metastatic PCa.
Tables
Patient no. Age (y) Baseline PSA (ng/mL) Dates of 99mTc-MIP scans Date of original diagnosis Prostatectomy Prior radiation therapy 1 66 4.3 3/23/11; 4/6/11 12/2/08 No No 2 71 8.9 3/3/11; 3/17/11 6/11/08 Yes (2008) Yes (2009); 7,020 cGy 3 66 22.4 3/8/11; 3/22/11 7/17/02 No Yes (2004); dose not available 4 62 3.3 4/1/11; 4/15/11 11/28/07 No No 5 68 7.3 4/7/11; 4/25/11 5/28/08 No No 6 76 48.4 5/11/11; 5/25/11 7/29/92 No Yes (2010); 6,600 cGy - TABLE 2
Blood Pharmacokinetic Analysis of 99mTc-MIP-1404 and 99mTc-MIP-1405 in Healthy Subjects and Patients with PCa
99mTc-MIP-1404 99mTc-MIP-1405 Pharmacokinetic parameter Healthy subject Patient Healthy subject Patient Tmax (h) 0.04 ± 0.02 0.03 ± 0.00 0.06 ± 0.03 0.05 ± 0.03 Cmax (h) 0.72 ± 0.36 0.87 ± 0.33 0.58 ± 0.24 0.60 ± 0.15 AUC(0-∞) (h × 37 KBq [μCi]/mL) 0.95 ± 0.32 1.34 ± 0.59 1.37 ± 0.51 1.44 ± 0.49 Clearance (mL/h/kg) 283 ± 100 198 ± 70 200 ± 45 181 ± 104 Vss (mL/kg) 4,020 ± 1,499 3,356 ± 1,371 938 ± 216* 824 ± 602* T1/2 elimination (h) 13.53 ± 2.18 15.26 ± 1.83 5.68 ± 0.97* 5.12 ± 0.84* MRT(0-∞) (h) 14.29 ± 3.29 16.95 ± 3.03 4.79 ± 1.06* 4.31 ± 0.67* T1/2α (h) 0.250 ± 2.5 0.12 ± 0.03 0.42 ± 0.30 0.21 ± 0.09 T1/2β (h) 13.2 ± 2.79 13.87 ± 1.37 5.51 ± 0.79* 5.03 ± 0.81* ↵* These values for 99mTc-MIP-1405 are statistically (P < 0.05) significant, compared with values obtained for 99mTc-MIP-1404.
Cmax = maximum concentration in plasma; AUC(0-∞) = area under the curve; Vss = steady-state volume of distribution; MRT(0-∞) = mean residence time; T1/2α = distribution half-life; T1/2β = elimination half-life.
99mTc-MIP-1404 99mTc-MIP-1405 Organ mGy/MBq mGy/740 MBq Rad/20 mCi mGy/MBq mGy/740 MBq Rad/20 mCi Kidneys 7.33E–02 54.24 5.42 3.63E–02 26.86 2.69 Salivary glands (77 g) 5.24E–02 38.78 3.88 3.01E–02 22.27 2.23 Spleen 2.18E–02 16.13 1.61 9.94E–03 7.36 0.74 Thyroid 1.95E–02 14.43 1.44 1.33E–02 9.84 0.98 Liver 1.61E–02 11.91 1.19 6.68E–03 4.94 0.49 Upper large intestine wall 1.61E–02 11.91 1.19 1.25E–02 9.25 0.93 Urinary bladder wall 1.27E–02 9.40 0.94 4.34E–02 32.12 3.21 Lower large intestine wall 1.16E–02 8.58 0.86 1.08E–02 7.99 0.80 Small intestine 1.04E–02 7.70 0.77 8.30E–03 6.14 0.61 Gallbladder wall 9.70E–03 7.18 0.72 5.54E–03 4.10 0.41 Adrenals 8.87E–03 6.56 0.66 4.95E–03 3.66 0.37 Pancreas 8.36E–03 6.19 0.62 4.81E–03 3.56 0.36 Osteogenic cells 8.36E–03 6.19 0.62 6.44E–03 4.77 0.48 Lungs 6.52E–03 4.82 0.48 3.88E–03 2.87 0.29 Ovaries 6.37E–03 4.71 0.47 6.51E–03 4.82 0.48 Uterus 5.98E–03 4.43 0.44 8.34E–03 6.17 0.62 Stomach wall 5.74E–03 4.25 0.42 3.72E–03 2.75 0.28 Heart wall 5.61E–03 4.15 0.42 3.53E–03 2.61 0.26 Red marrow 4.08E–03 3.02 0.30 3.02E–03 2.23 0.22 Muscle 3.52E–03 2.60 0.26 2.86E–03 2.12 0.21 Thymus 3.05E–03 2.26 0.23 2.22E–03 1.64 0.16 Testes 2.59E–03 1.92 0.19 3.20E–03 2.37 0.24 Breasts 2.27E–03 1.68 0.17 1.60E–03 1.18 0.12 Skin 2.01E–03 1.49 0.15 1.58E–03 1.17 0.12 Brain 1.23E–03 0.91 0.09 9.14E–04 0.68 0.07 Total body 4.46E–03 3.30 0.33 3.29E–03 2.43 0.24 Effective dose equivalent 1.25E–02 9.25 0.93 1.01E–02 7.47 0.75 Effective dose (mSv/MBq) 8.78E–03 6.50 0.65 7.87E–03 5.82 0.58
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