1150
Yang WJ, et al. Sci China Chem July (2011) Vol.54 No.7
of methanol and refluxed under stirring. Then 0.2 g hydra-
zine hydrate was added, and the mixture was refluxed for 3
h. After addition of conc. HCl to adjust the pH to 6, a white
solid of phthalic acid hydrazide was precipitated. After fil-
tration, the pH of liquid phase was adjusted to about 12 with
3 mol/L NaOH. The solvent was then evaporated in vacuo,
and 5 mL water was added. Extracted three times with me-
thylene dichloride (3 mL for each extraction), and the com-
bined organic phases were extracted three times with water
(3 mL for each extraction). The organic phases were dried
over anhydrous Na2SO4. Removal of the solvent gave 3-3 as
41.48% H 6.91% N 10.37%. Found: C 41.77% H 7.44% N
10.36%.
MPP4DTC: (NaC16N3H24OS2·0.5H2O) m/z = 338 (M+,
calcd m/z 361). Calcd: C 51.89% H 6.76% N 11.35%.
Found: C 51.55% H 6.79% N 11.15%.
IR (KBr) (cm1): 936–958 (C=S), for MPP2DTC to
MPP6DTC.
2.3 Preparation of 99mTcN-MPPnDTC
The 99mTcN-MPPnDTC was prepared by a two-step proce-
dure. 1 mL saline-containing Na99mTcO4 (about 185 MBq)
was added into a DTCZ kit and heating under N2 at 100 °C
for 15 min to obtain the [99mTcN]2+ intermediate. Then 0.2 mL
1
colorless oil, yield 71%. H NMR(CDCl3): 6.876–7.076(m,
4H, phenyl-OCH3), 3.889(s, 3H, OCH3), 3.126, 2.694(m,
8H, N(CH2CH2)2N), 2.822–2.849(t, 2H, NH2-CH2),
2.505–2.534(t, 2H, NH2CH2CH2), 1.891(s, 2H, NH2CH2),
1.703–1.759(m, 2H, NH2CH2 CH2CH2).
[
99mTcN]2+ (about 37 MBq) intermediate was added to the
MPPnDTC (2 mg ligand dissolved in 0.2 mL water) and
incubated for 20 min at room temperature.
Sodium hydroxide (2.41 mmol) was dissolved in 10 mL
water and cooled in an ice-salt bath. Then 0.6 g 3-3 (2.41
mmol) was added with stirring, after that 0.2 g carbon disul-
fide (2.65 mmol) was added immediately. The mixture was
stirred for 2 h in an ice-salt bath. Most of the solvent was
removed under reduced pressure, and the precipitate col-
lected by filtration. The white crude product was recrystal-
lized from ethanol to give the compound MPP3DTC, yield
78%. (NaC15N3H22OS2·2.5H2O) ESI-MS: m/z 324.2 (M+,
calcd m/z 347). Calcd.: C 45.92% H 6.89% N 10.71%. Found:
C 45.90% H 6.38% N 10.56%. 1HNMR (500 MHz, D2O,):
7.08–6.91 (m, 4H, CH3O-phenyl-N), 3.76(s, 3H, OCH3),
3.49–3.46(t, 2H, CS2NHCH2), 2.90–2.45(m, 8H, N(CH2-
CH2)2N), 2.43–2.40(m, 2H, CH2-piperazine), 1.79–1.73(m,
2H, CH2CH2CH2). IR (KBr) (cm1): 943.8 (C=S)
The [99mTcN]2+ intermediate and final 99mTcN-MPPnDTC
complex were characterized by both TLC and HPLC. TLC
was performed on a polyamide film with saline and metha-
nol/methylene dichloride (v/v = 9:1) as the mobile phase.
RP-HPLC was performed on a Alltech system with Kroma-
sil C-18 column (4.6 × 250 mm, 5 m). The flow rate was
1 mL/min with water (solvent A) and methanol (solvent B)
were used as the mobile phase in the following gradient
(0–10 min, B conc. 60%–100%; 10–30 min, B conc. 100%).
99mTcN-MPPnDTC was purified with semi-preparative
column Venusil MP-C18 (10 × 250 mm, 5 m). The flow
rate was set at 3 mL/min with above-described gradient.
2.4 Preparation of 99mTc(CO)3-MPP3DTC
The 99mTc(CO)3-MPP3DTC was prepared by a two-step
procedure.
Other products were characterized by:
1HNMR (500 MHz, D2O, , ppm): MPP2DTC: 6.91–7.09
(m, 4H, CH3O-phenyl-N), 3.76(s, 3H, OCH3), 3.67–3.70(t,
2H, CS2NHCH2), 2.90–2.45(m, 8H, N(CH2CH2)2N), 2.43–
2.40(m, 2H, CH2-piperazine).
[
99mTc(CO)3(H2O)3]+ was prepared by adding 1 mL of
99mTcO4 eluted from a commercial generator (37 MBq) to a
10 mL vial containing potassium boranocarbonate (3 mg),
sodium potassium tartrate tetrahydrate (6.7 mg), and potas-
sium tetraborate pentahydrate (5.2 mg). Then the solution
was heated for 15 min in boiling water under N2. After
cooling down to room temperature, the sample was ana-
lyzed on TLC and HPLC.
MPP4DTC: 7.08–6.91 (m, 4H, CH3O-phenyl-N), 3.76(s,
3H, OCH3), 3.47–3.44(t, 2H, CS2NHCH2CH2), 2.96–2.40(m,
8H, N(CH2CH2)2N), 2.43–2.40(m, 2H, CH2-piperazine),
1.56–1.46(m, 4H, CH2CH2CH2-piperazine).
MPP5DTC: 7.057–6.910 (m, 4H, CH3O-phenyl-N), 3.749
(s, 3H, -OCH3), 3.409–3.436(t, 2H, CS2NHCH2CH2), 2.96–
2.40(m, 8H, N(CH2CH2)2N), 2.351–2.382(t, 2H, CH2-pipera-
zine), 1.524–1.554(m, 2H, CH2CH2CH2CH2-piperazine),
1.453–1.467(m, 2H, CH2CH2CH2-piperazine), 1.249–1.278
(m, 2H, CH2CH2-piperazine).
MPP6DTC: 7.057–6.910 (m, 4H, CH3O-phenyl-N), 3.749
(s, 3H, -OCH3), 3.409–3.436(t, 2H, CS2NHCH2CH2), 2.96–
2.40(m, 8H, N(CH2CH2)2N), 2.351–2.382(t, 2H, CH2-
piperazine), 1.524–1.554(m, 2H, CH2CH2CH2CH2-piperazine),
1.453–1.467(m, 2H, CH2CH2CH2-piperazine), 1.249–1.278
(m, 2H, CH2CH2-piperazine).
The pH value of [99mTc(CO)3(H2O)3]+ intermediate was
adjusted to 7. Then 2 mg MPP3DTC was added to the
above solution. The final complex 99mTc(CO)3-MPP3DTC
was obtained after 30 min incubation at room temperature.
The [99mTc(CO)3(H2O)3]+ intermediate and final 99mTc
(CO)3-MPP3DTC complex were characterized by both TLC
and HPLC, and purified with semi-preparative HPLC.
2.5 Octanol/water partition coefficient
The partition coefficient of the complex was determined by
measuring the activity that partitioned between the n-octanol
and aqueous phosphate buffer (0.025 mol/L, pH 7.4) under
ESI-MS and elemental analyses: MPP2DTC: (NaC14N3-
H20OS2·4H2O) m/z 310.1 (M+, calcd m/z 333). Calcd: C