Article Figures & Data
Figures
- FIGURE 1.
Chemical structures of 111In-PSMA-I&T and 99mTc-MAS3/mas3-y-nal-k-Sub-KuE.
- FIGURE 2.
Synthesis of MAS3-y-nal-k-Sub-KuE (5) and mas3-y-nal-k-Sub-KuE (6, PSMA-I&S). (A) Piperidine (20%) in NMP, Fmoc-D-2NaI-OH, HOBt, TBTU, DIPEA, [NMP]. (B) Piperidine (20%) in NMP, Fmoc-D-Tyr(tBu)-OH, HOBt, TBTU, DIPEA, [NMP]. (C) Piperidine (20%) in NMP, Fmoc-D-Ser(tBu)-OH, HOBt, TBTU, DIPEA, [NMP]. (D) Piperidine (20%) in NMP, S-Trityl-mercaptoacetic acid, HOBt, TBTU, DIPEA, [NMP]. (E) DCM/TFE/acetic acid (6/3/1, (v/v)). (F) Piperidine (20%) in NMP, Fmoc-L-Ser(tBu)-OH, HOBt, TBTU, DIPEA, [NMP]. (G) Sub(OPfp)2, TEA, [DMF]. (H) 3, TEA, [DMF]. (I) TFA. (J) 4, TEA, [DMF].
- FIGURE 3.
(Left) Kinetics of PSMA-mediated total cellular uptake and internalization of 99mTc-PSMA-I&S (0.2 nM) into LNCaP cells (37°C) (mean ± SD [n = 3]). (Right) Kinetics of PSMA-mediated internalization of 99mTc-PSMA-I&S (0.2 nM) and reference (125I-BA)KuE (0.2 nM) into LNCaP cells (37°C) (mean ± SD [n = 3]).
- FIGURE 4.
In vivo stability of 99mTc-PSMA-I&S and 99mTc-6 in CD-1 nu/nu mice. Radio–high-performance liquid chromatograms of intact tracer (before injection) and cell-free blood, urine, and kidney homogenate samples collected 1 h after injection of respective radioligands.
- FIGURE 5.
68Ga-HBED-CC PSMA PET (A; maximum-intensity projection, 1 h after injection) and 99mTc-PSMA-I&S whole-body planar scintigraphy (B–E) were performed in a PCa patient with metastatic, hormone-refractory disease. (B–E) Whole-body planar scintigraphy at 1 (B), 3 (C), 5 (D), and 21 h (E) after injection of approximately 500 MBq of 99mTc-PSMA-I&S.
- FIGURE 6.
Preoperative 68Ga-HBED-CC PSMA PET/MR (A–D) and 99mTc-PSMA-I&S SPECT/CT (E–H). 68Ga-HBED-CC PSMA PET/MR shows iliac (A and B) and inguinal lymph node metastases (C and D). 99mTc-PSMA-I&S SPECT/CT at 12 h after injection reveals intense tracer uptake in same lymph nodes.
Tables
- TABLE 1
IC50, Internalization, and Lipophilicity of Ga-, Lu-, and In-PSMA-I&T (22,24) and of Novel Unlabeled and Labeled MAS3/mas3-y-naI-k(Sub-KuE) Analogs
Ligand IC50 (nM) Specific internalization (% of reference)* Lipophilicity (log POW) Ga-PSMA-I&T 9.4 ± 2.9 68GaPSMA-I&T 59 ± 2 −4.3 Lu-PSMA-I&T 7.9 ± 2.4 177LuPSMA-I&T 76 ± 2 −4.1 In-PSMA-I&T 7.5 ± 1.5 111InPSMA-I&T 104 ± 7 −4.5 Mas3-y-nal-k(Sub-KuE) = PSMA-I&S (5) 39.7 ± 1.2 99mTcPSMA-I&S 93 ± 3 −3.0 MAS3-y-naI-k(Sub-KuE) (6) 47.6 ± 2.5 99mTc-6 78 ± 2 −2.9 Re-PSMA-I&S (Re-5) 15.5 ± 2.8 Re-MAS3-y-naI-k(Sub-KuE) (Re-6) 12.4 ± 0.8 ↵* Specific internalization of reference compound (125I-BA)KuE was determined in a parallel experiment and used for data normalization.
OW = octanol water.
- TABLE 2
Biodistribution of 99mTc-PSMA-I&S and Reference 111In-PSMA-I&T (24) in LNCaP Tumor–Bearing CB-17 Severe Combined Immunodeficiency Mice at 1 Hour After Injection
Organ 111In-PSMA-I&T 99mTc-PSMA-I&S 99mTc-PSMA-I&S + PMPA Blood 0.24 ± 0.05 1.73 ± 0.50 1.22 ± 0.27 Heart 0.37 ± 0.08 0.94 ± 0.31 0.54 ± 0.12 Lung 1.78 ± 0.18 1.61 ± 0.80 1.20 ± 0.43 Liver 0.26 ± 0.04 1.58 ± 0.24 0.76 ± 0.18 Spleen 47 ± 13 47 ± 17 1.18 ± 0.32 Pancreas 0.59 ± 0.18 0.95 ± 0.19 0.31 ± 0.09 Stomach 0.31 ± 0.16 5.55 ± 0.88 2.64 ± 1.36 Intestines 0.15 ± 0.01 2.46 ± 0.14 2.44 ± 0.33 Kidney 191 ± 24 186 ± 23 9.78 ± 2.95 Muscle 0.19 ± 0.01 0.39 ± 0.15 0.20 ± 0.06 LNCaP tumor 8.07 ± 1.06 8.28 ± 3.27 1.83 ± 0.44 SCID = severe combined immunodeficiency.
Data are given in percentage injected dose per gram and are mean ± SD (n = 3–5 animals per group).
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