Evaluation and comparison of 99mTc-labeled d-glucosamine derivatives with different 99mTc cores as potential tumor imaging agents

Article abstract of DOI:10.1002/aoc.6008

Isocyanide is a strong coordination ligand that can coordinate with [^99mTc(I)(CO)₃]⁺ core and [^99mTc(I)]⁺ core to produce stable ^99mTc complexes, therefore developing a ^99mTc-lab

Full text of DOI:10.1002/aoc.6008

Received: 14 August 2020
DOI: 10.1002/aoc.6008
Revised: 27 August 2020
Accepted: 29 August 2020
F U L L P A P E R
Evaluation and comparison of 99mTc-labeled D-glucosamine
derivatives with different 99mTc cores as potential tumor
imaging agents
Xuran Zhang
| Qianqian Gan | Qing Ruan | Di Xiao | Junbo Zhang
Key Laboratory of Radiopharmaceuticals
of Ministry of Education, College of
Chemistry, Beijing Normal University,
Beijing, 100875, China
Isocyanide is a strong coordination ligand that can coordinate with [99mTc(I)
(CO)3]+ core and [99mTc(I)]+ core to produce stable 99mTc complexes, therefore
developing a 99mTc-labeled isocyanide complex for single-photon emission
computed tomography (SPECT) imaging is considered to be of great interest.
In order to develop potential tumor imaging agents with satisfied tumor uptake
and suitable pharmacokinetic properties in vivo, a novel D-glucosamine
isocyanide derivative, 4-isocyano-N-(2,4,5-trihydroxy-6-(hydroxymethyl)tetra-
hydro-2H-pyran-3-yl)butanamide (CN3DG), was synthesized and radiolabeled
with [99mTc(I)]+ and [99mTc(CO)3]+ cores to obtain [99mTc(CN3DG)6]+ and
Correspondence
Junbo Zhang, Key Laboratory of
Radiopharmaceuticals of Ministry of
Education, College of Chemistry, Beijing
Normal University, Beijing 100875, China.
Email: zhjunbo@bnu.edu.cn
Funding information
[
99mTc(CO)3(CN3DG)3]+ in high radiolabeling yields (>95%). Both of the com-
China Postdoctoral Science Foundation,
Grant/Award Number: 212400211; Beijing
Municipal Science and Technology
Commission, Grant/Award Number:
Z181100002218033; National Natural
Science Foundation of China, Grant/
Award Number: 21771023
plexes showed good hydrophilicity and great stability in vitro. Cell uptake
studies performed in S180 cells demonstrated they were transported into cells
by glucose transporters. Biodistribution studies of the two complexes in mice
bearing S180 tumor showed they had high tumor uptakes and rapid clearance
from muscle and blood so that the tumor/blood and tumor/muscle
ratios were high. By comparison, [99mTc(CN3DG)6]+ was superior to [99mTc
(CO)3(CN3DG)3]+ in regard to tumor uptake, tumor/blood and tumor/liver
ratios. S180 tumors could be seen clearly from the SPECT/CT images with [99mTc
(CN3DG)6]+. Considering its favorable properties, [99mTc(CN3DG)6]+ would be a
promising tumor imaging agent and needs to be further studied.
K E Y W O R D S
D-glucosamine, isocyanide, radiopharmaceutical, SPECT, tumor imaging
1 | INTRODUCTION
Fluoro-2-deoxy-D-glucose (18F-FDG) is a widely used PET
tracer for clinical tumor imaging due to its similar
As cancer is becoming the leading disease that threatens
people's health and lives, early diagnosis of cancers plays
an important role in preventing their progression and
making treatment options personally. Positron emission
tomography (PET) and single-photon emission computed
tomography (SPECT) are the main noninvasive nuclear
imaging modalities that used in cancer diagnosis, staging
and monitoring the chemotherapy response.[1,2] 2-[18F]
chemical structure to glucose that can be recognized by
glut transporters (GLUTS) and transported into cancer
cells.[3–6] However, the short half-life (T1/2 = 110 min) of
18F and its expensive production cost by a cyclotron
limited its wide application.
Technetium-99m accounts for about 90% SPECT
imaging studies in the world because of its suitable
nuclide properties (T1/2 = 6.02 h, Eγ = 140 keV) and
Appl Organomet Chem. 2020;34:e6008.
wileyonlinelibrary.com/journal/aoc
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ZHANG ET AL.
inexpensive diagnostic cost. Recently, many 99mTc-
labeled glucose derivatives have been developed and
evaluated as tumor imaging agents.[7–17] Among them,
99mTc-ethylenedicysteine-deoxyglucose (99mTc-ECDG) is
the most promising metabolic imaging agent and is
ongoing its phase III study.[18–20] However, the
tumor/blood ratio of 99mTc-ECDG in A549 tumors was
not satisfactory owing to its high blood uptake and slow
clearance.
radioactivity detector using an analytical column (18C,
Kromasil, 100–5 μm, 250 × 4.6 mm). The HPLC gradient
elution method: System 1 (A, 0.1% trifluoroacetate in
water; B, 0.1% trifluoroacetate in acetonitrile) was
0–2 min, 10% B; 2–10 min, 10–90% B; 10–15 min, 90% B;
15–20 min, 90–10% B. System 2 (A, 0.1% trifluoroacetate
in water; B, 0.1% trifluoroacetate in methanol) was
0–2 min, 10% B; 2–10 min, 10–90% B; 10–15 min, 90% B;
15–20 min, 90–10% B. Radioactivity (CPM) was recorded
on a WIZARD2® 2480 PerkinElmer system. SPECT/CT
images were acquired on a Trifoil Imaging Triumph
Scanner (Triumph SPECT/CT, console-gr157). Animal
studies were carried out in compliance with the Regula-
tions on Laboratory Animals of Beijing Municipality and
the guidelines of the Ethics Committee of Beijing Normal
University.
In our previous studies, a glucose derivative with an
isonitrile group (CN5DG) was synthesized and
radiolabeled with
[
99mTc(I)]+ core to prepare
99mTc-CN5DG.[21] 99mTc-CN5DG exhibited a certain
tumor uptake and favorable blood and muscle clearance;
however, its tumor uptake needs to be increased, and its
initial blood uptake needs to be decreased to obtain better
SPECT images. Bearing in mind the different 99mTc cores,
lipophilicity and overall size are the main factors
influencing the biodistribution results of the resulting
99mTc complexes[22–26]; in this study, 4-isocyano-N-
(2,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-
3-yl)butanamide (CN3DG) (Scheme 1) with less
methylene number was synthesized and radiolabeled
with [99mTc(I)]+ core and [99mTc(I)(CO)3]+ core to obtain
2.2 | Chemistry and radiochemistry
2.2.1 | 6-Isocyano-N-(2,4,5-trihydroxy-
6-(hydroxymethyl)tetrahydro-2H-pyran-
3-yl)hexanamide (CN3DG, 5)
[
99mTc(CN3DG)6]+
(Figure 1). The feasibility of [99mTc(CN3DG)6]+ and
99mTc(CO)3(CN3DG)3]+ as tumor imaging agents were
and
[
99mTc(CO)3(CN3DG)3]+
First, compound 4 was synthesized according to the pub-
lished literature,[21] and the synthetic route was shown in
Scheme 1. CN3DG (5) was synthesized as follows:
D-glucosamine hydrochloride (117 mg, 0.54 mmol) and
sodium hydroxide (22 mg, 0.54 mmol) were dissolved in
methanol (20 ml) and stirred at room temperature for
30 min. To this stirred mixture, 4 (156 mg, 0.60 mmol)
was added and the reaction mixture continued to stir at
room temperature overnight. The solvent was removed
under reduced vacuum, and the residue was washed with
acetonitrile to obtain the crude product; then, silica gel
column chromatography was used to obtain compound
[
evaluated and compared in rodents in this paper.
2 | EXPERIMENTAL SECTION
2.1 | Materials and methods
All chemical reagents and solvents were purchased from
commercial companies and were used directly. 99mTcO4
−
was obtained from a 99Mo/99mTc generator. 1H-NMR and
13C-NMR data were acquired on a Bruker spectrometer
(Avance 500, 400 MHz, USA). The MS spectrum was
recorded on a Bruker solariX ESI mass spectrometer.
Radiochemical purity was analyzed by HPLC equipped
with a Waters 2489 UV system and a Gabi raytest
5 as a white powder (85 mg, 57%). IR (KBr)/cm−1
:
3294.56 ( OH), 2148.79 ( NC), 1645.35 ( C O).
1H-NMR(400 MHz, D2O): δ (ppm) 3.59–3.77 (m, 5H),
3.31–3.42 (m, 4H), 2.31–2.35 (m, 2H), 1.85 (s, 2H).
13C-NMR (100 MHz, D2O) δ 175.74, 175.52, 151.53
(t, J = 7 Hz, NC), 94.95, 90.85, 75.94, 73.81, 71.58, 70.65,
SCHEME 1 Synthesis of CN3DG. (a) DMF,
formic acid, reflux; (b) 2,3,5,6-tetrafuorophenol,
EDCI, CH2Cl2, rt; (c) Burgess reagent, CH2Cl2, rt;
and (d) sodium hydroxide, CH3OH, rt

ZHANG ET AL.
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FIGURE 1 Chemical structures of
CN5DG and CN3DG and their
corresponding metal complexes
70.14, 69.94, 60.76, 60.61, 56.59, 54.34, 54.05, 40.93
(t, J = 6 Hz, NCH2), 32.58, 32.41, 24.67, 24.58. HRMS
(ESI): [C11H18N2O6Na]+: m/z calcd. for [M + Na]+
297.1057, found 297.1052.
(0.5 mg), 30-μl SnCl2Á2H2O (1 mg ml−1) were added. The
pH value of the solution was adjusted to 5–6 by using
0.1 M NaOH. CN3DG (1 mg) and 99mTcO4 (1–10 mCi)
−
were then added, successively. The vial was sealed and
heated at 100ꢀC for 20 min. After cooling to room tem-
perature, 10 μl of the labeling solution was injected into a
radio-HPLC system for radiochemical purity determina-
tion (System 2).
2.2.2 | Preparation of
[Re(CO)3(CN3DG)3]+
For the preparation of
[
99mTc(CO)3(H2O)3]+ was firstly synthesized as radio-
[
99mTc(CO)3(CN3DG)3]+,
[Re(CO)3(CN3DG)3]+ was synthesized according to the
previous literature.[26] [Re(CO)5]Br (10 mg) was dissolved
in 5 ml of purified water in a 10-ml penicillin vial, and
the mixture was heated at 100ꢀC overnight to obtain the
intermediate [Re(CO)3(H2O)3]+. Then, 0.5 ml of the
above mixture was added to a 10-ml penicillin vial, and
CN3DG (50 mg) was added and heated at 100ꢀC for 3 h.
After cooling to room temperature, [Re(CO)3(CN3DG)3]+
was purified by HPLC using System 1. 1H-NMR
(400 MHz, D2O): δ (ppm) 3.54–3.82 (m, 21H), 3.23–3.47
(m, 6H), 2.23–2.42 (m, 6H), 1.87–2.01 (m, 6H). HRMS
(ESI): [Re(C11H18N2O6)3(CO)3]+: m/z calcd. for
ReC36H54N6O21 1093.2896, found 1093.2891.
labeling intermediate according to the published litera-
ture.[26] The pH value of the intermediate was adjusted to
7–8 by using 1 M HCl, and it was added to a penicillin
vial containing 1-mg CN3DG. The sealed vial was heated
at 100ꢀC for 20 min. After cooling to room temperature,
10 μl of the labeling solution was injected into a radio-
HPLC system for radiochemical purity determination
(System 1).
2.3 | Water/n-octanol partition coefficient
determination
[
99mTc(CN3DG)6]+ and [99mTc(CO)3(CN3DG)3]+ sepa-
2.2.3 | Radiolabeling
rated from the HPLC system were used for partition coef-
ficient determination. The separated complexes were
concentrated in vacuo to remove the organic solvent and
then 50 μl of each sample (1.85 MBq) was added to an
For preparation of [99mTc(CN3DG)6]+, to a 10-ml penicil-
lin vial containing sodium citrate (1 mg) and L-cysteine

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ZHANG ET AL.
equal volume mixture (2 ml:2 ml) of PBS (0.1 M, pH 7.4)
and n-octanol. The mixed solution was vortexed for
5 min and left to stand for 2 min, then the mixture was
centrifuged for 5 min at 2000 rpm. Three samples (100 μl
for each) from each layer were collected, and the radioac-
tivity was measured on an automatic γ-counter. The
partition coefficient (P) was calculated as follows:
P = (radioactivity in octanol/radioactivity in aqueous
layer). The partition coefficient (Log P) was reported as
average of three experiments standard deviation (SD).
(CO)3(CN3DG)3]+) via the tail vein. The animals were
sacrificed at 0.5, 1, and 2 h post injection (n = 5). The
interested organs were removed and weighted, and the
radioactivity was collected on a gamma counter. The
results were presented as the percentage of the injected
dose per gram (%ID g−1). The data were expressed as
average SD of five animals.
2.7 | SPECT/CT imaging
A total of 0.1–0.2 ml of [99mTc(CN3DG)6]+ (74 MBq) was
injected into S180 tumor-bearing mice via the tail vein
(n = 3) and imaged at 0.5, 1, and 2 h post injection. For
2.4 | Stability studies in vitro
Stability studies for each radiolabeled complex separated
by the HPLC were carried out in saline and mice serum
in vitro. Fifty microliters of each complex (370 kBq) was
mixed with 1 ml of saline or 500 μl of freshly prepared
mice serum. After 6 h in saline, 10 μl of each complex
was analyzed by radio-HPLC for radiochemical purity
determination (n = 3). For HPLC analysis of samples
in mice serum for 2 h, 300 μl of acetonitrile was added
into 200 μl of the incubated serum to precipitate the
protein. After being centrifuged at 10,000 g for 5 min, the
supernatant was collected and concentrated, and
the remaining solution was analyzed with the radio-
HPLC system.
[
99mTc(CO)3(CN3DG)3]+, animals were imaged at 1 h
post injection. The animals received
a standard
SPECT/CT protocol (MMP919 collimator, 20 min of
SPECT scan followed by 4 min of CT scan) and being
anesthetized with 1.5% isoflurane during the process. The
SPECT/CT images were reconstructed by a HiSPECT
software and analyzed with VivoQuant 2.5 software.
2.8 | Statistical analysis
The cell uptake data and the biodistribution data were
calculated and analyzed with Microsoft Excel and Prism
5.01. All data were presented as average SD. To com-
pare differences between two data, the Student's t test
was used. P < 0.05 indicated a statistically significant
difference.
2.5 | Cell uptake studies
The cell uptake blocking studies were conducted
according to the previous published literatures.[20,21] S180
cells were used for cell uptake studies; 3 × 106 cells were
suspended in 0.5 ml of glucose-free medium containing
D-glucose (2 mg) or L-glucose (2 mg) (each group has five
tubes) in 2-ml centrifuge tubes. Then, [99mTc(CN3DG)6]+
(0.5 ml, 740 kBq) or [99mTc(CO)3(CN3DG)3]+ (0.5 ml,
740 kBq) was added, and the mixtures were incubated at
37ꢀC for 4 h. After 4-h incubation, the tubes were cen-
trifuged and the supernatant were removed. The precipi-
tated cells were washed with cold phosphate-buffered
saline (pH 7.4, 0.1 M) twice (2 × 1 ml), and the cell
uptake radioactivity was measured by a γ-counter
(PerkinElmer, WIZARD 2480).
3 | RESULTS AND DISCUSSION
3.1 | Chemistry and radiolabeling
chemistry
CN3DG was prepared by reacting D-glucosamine hydro-
chloride with isonitrile bearing activated ester (4) under
alkaline conditions (Scheme 1) overnight. In the last step,
4 was 1.2 times more than D-glucosamine hydrochloride
to make D-glucosamine hydrochloride react completely.
The excessive ester 4 could be removed easily by washing
with acetonitrile. The chemical structure of CN3DG was
confirmed by 1H-NMR, 13C-NMR, IR, and HRMS
(Supporting Information).
2.6 | Biodistribution studies
[
99mTc(CN3DG)6]+ and
[
99mTc(CO)3(CN3DG)3]+
were obtained in high radiochemical purity (>95%) veri-
fied by HPLC with the retention time 9.71 and 10.48 min
Biodistribution data were collected according to the pub-
lished literature.[22] Kunming female mice bearing S180
tumors (0.5–1.0 cm in diameter) were injected 74 kBq of
99mTc-labeled complexes ([99mTc(CN3DG)6]+ or [99mTc
(Figure 2). Under the same conditions, the retention time
of 99mTcO4
and
[
99mTc(CO)3(H2O)3]+ were 3.93
−
and 12.17 min, respectively. The specific radioactivity

ZHANG ET AL.
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FIGURE 2 (a) HPLC profiles of [99mTc
(CN3DG)6]+ and (b) co-injection HPLC profiles
of [Re(CO)3(CN3DG)3]+ and [99mTc
(CO)3(CN3DG)3]+
FIGURE 3 Stability studies of (a,b)
[
99mTc(CN3DG)6]+ and (c,d) [99mTc
(CO)3(CN3DG)3]+ in vitro
for the probes was 10.14–101.37 GBq mmol−1. In
order to confirm the chemical structure of [99mTc
(CO)3(CN3DG)3]+, the corresponding Re coordinated
(CO)3(CN3DG)3]+ were −4.01 0.17 and −2.65 0.20,
demonstrating both tracers were hydrophilic. Moreover,
[
99mTc(CN3DG)6]+ was more hydrophilic than [99mTc
1
complex was synthesized and confirmed by H-NMR, IR,
(CO)3(CN3DG)3]+, possibly because [99mTc(CN3DG)6]+
had a structure with six CN3DG ligands whereas
and HRMS (Supporting Information). As shown in
Figure 2, the HPLC retention time of
(CO)3(CN3DG)3]+ (10.48 min) matched with that of [Re
(CO)3(CN3DG)3]+ (9.92 min), suggesting 99mTc
[
99mTc
[
99mTc(CO)3(CN3DG)3]+ had only three CN3DG
ligands.
[
(CO)3(CN3DG)3]+ had similar structure with [Re
(CO)3(CN3DG)3]+ as shown in Figure 2b. We tried to
prepare [Re (CN3DG)6]+; unfortunately, we failed to
obtain the pure Re complex. The proposed structure of
3.3 | Cell uptake studies
As shown in Figure 4, 2-mg D-glucose could significantly
block the uptake value of [99mTc(CN3DG)6]+ and [99mTc
(CO)3(CN3DG)3]+ in S180 tumor cells after 4-h
co-incubation, whereas 2-mg L-glucose had little affects.
These findings suggested that the two complexes could
be transported into S180 cells by glucose transporters.
[
99mTc(CN3DG)6]+ was shown in Figure 1b, which was
similar to that of 99mTc-CN5DG as shown in Figure 1a.
3.2 | In vitro stability and the
water/octanol partition coefficients studies
Both [99mTc(CN3DG)6]+ and [99mTc(CO)3(CN3DG)3]+
were stable in saline for 6 h and in mice serum for 2 h
examined by HPLC shown in Figure 3. The partition
coefficients (Log P) of [99mTc(CN3DG)6]+ and [99mTc
3.4 | Biodistribution studies
The biodistribution data of [99mTc(CN3DG)6]+ and
[
99mTc(CO)3(CN3DG)3]+ in S180 tumor-bearing mice

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ZHANG ET AL.
FIGURE 4 Cell uptake data of (a) [99mTc
(CN3DG)6]+ and (b) [99mTc(CO)3(CN3DG)3]+ in
S180 cells after co-incubation with D-glucose or
L-glucose for 4 h in vitro. *P < 0.05
FIGURE 5 Biodistribution data of (a) [99mTc(CN3DG)6]+ and (b) [99mTc(CO)3(CN3DG)3]+. (c) Comparison of biodistribution data of
99mTc(CN3DG)6]+, [99mTc(CO)3(CN3DG)3]+, and 99mTc-CN5DG. (d) Comparison of the tumor/muscle, tumor/blood, and tumor/liver ratios
of [99mTc(CN3DG)6]+, [99mTc(CO)3(CN3DG)3]+, and 99mTc-CN5DG. *P < 0.05, **P < 0.01
[
were shown in Figure 5a,b. Both complexes had a high
tumor uptake at 30 min post injection and decreased as a
function of time. The highest uptake tissue for both
tracers was kidney, suggesting the key clearance route
was through urinary tract.
0.23 0.03%ID g−1 vs. 1.06 0.23%ID g−1, *P < 0.05) and
blood uptake (1 h after injection, 0.12
0.03%ID g−1
vs. 0.42
0.10%ID g−1 *P < 0.05). Low uptake in
,
stomach for both tracers demonstrated that they were
stable in vivo.
By comparison, [99mTc(CN3DG)6]+ had a slightly
higher tumor uptake and lower liver and blood uptakes,
resulting in higher tumor/blood and tumor/liver ratios.
These differences may attribute to their different chemi-
cal structures and lipophilicity. [99mTc(CN3DG)6]+ had
six CN3DG ligands and was more hydrophilic thus
making its lower liver uptake (1 h after injection,
Compared with the biodistribution data of 99mTc-
CN5DG at 1 h post injection, [99mTc(CN3DG)6]+ had
lower muscle uptake (0.27
CN5DG vs. 0.17
0.07%ID g−1 for [99mTc(CN3DG)6]+)
and blood uptake (0.55 0.17%ID g−1 for 99mTc-CN5DG
vs. 0.12
0.03%ID g−1 for [99mTc(CN3DG)6]+) whereas
the tumor uptake (1.07 0.21%ID g−1 for 99mTc-CN5DG
0.10%ID g−1 for 99mTc-

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FIGURE 6 Whole body single-photon emission computed tomography (SPECT)/CT images of (a) [99mTc(CN3DG)6]+ and (b) [99mTc
(CO)3(CN3DG)3]+ in S180 tumor-bearing mice (n = 3)
vs. 1.00
0.17%ID g−1 for [99mTc(CN3DG)6]+) of both
at 60 min post injection, but there were also higher
uptakes in gallbladder, liver, kidney, intestine, and blad-
der. From the SPECT images, the region of interest (ROI)
ratios of the tumor site versus corresponding nontumor
site for [99mTc(CN3DG)6]+ and [99mTc(CO)3(CN3DG)3]+
had no significant difference (Figure 5c). The
tumor/muscle, tumor/blood, and tumor/liver ratios of
[
99mTc(CN3DG)6]+ (7.31
1.18, 8.14
0.62) were higher than those of 99mTc-CN5DG
0.66, 2.00 0.31, and 2.84 0.33) (Figure 5d).
1.41, and
4.36
(4.21
were 6.54
0.42 and 4.23
0.94, respectively. These
This may attribute to the shorter carbon chain in the
structure of CN3DG, thus causing [99mTc(CN3DG)6]+
more hydrophilic (Log P = −4.01
CN5DG (Log P = −3.57 0.35).
results were in accordance with their biodistribution
data. It is reasonable to conclude that [99mTc(CN3DG)6]+
is more suitable for tumor detection than [99mTc
(CO)3(CN3DG)3]+, and it will be a promising candidate
as a tumor imaging agent.
0.17) than 99mTc-
3.5 | SPECT/CT imaging studies
4 | CONCLUSION
SPECT/CT scans of S180 tumor-bearing mice were taken
with [99mTc(CN3DG)6]+ (at 30, 60, and 120 min post
injection; Figure 6a) and
(at 60 min post injection; Figure 6b) using a small animal
SPECT/CT scanner. As for [99mTc(CN3DG)6]+, S180
tumors could be clearly seen from the images from 30 to
120 min after injection, and there were also high uptakes
in kidney and bladder. S180 tumor could also be seen
from the SPECT/CT images of [99mTc(CO)3(CN3DG)3]+
In this study, a novel D-glucosamine isocyanide (CN3DG)
is synthesized and radiolabeled with [99mTc(I)]+ and
[
99mTc(CO)3(CN3DG)3]+
[
99mTc(CO)3]+ to produce [99mTc(CN3DG)6]+ and [99mTc
(CO)3(CN3DG)3]+ in high radiochemical purity. Both of
the tracers are stable in saline and mice serum in vitro.
Cell uptake studies demonstrate that the two complexes
can be transported into cells through glucose trans-
porters. Both tracers have high tumor uptake in S180

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ZHANG ET AL.
tumor-bearing mice, and [99mTc(CN3DG)6]+ is superior
to [99mTc(CO)3(CN3DG)3]+. SPECT/CT studies demon-
strate that [99mTc(CN3DG)6]+ exhibits an obvious accu-
mulation in tumor sites and high target/nontarget ratios,
suggesting it is a promising tumor imaging agent.
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ACKNOWLEDGMENTS
This work is financially supported, in part, by the
National Natural Science Foundation of China
(21771023), the project of the Beijing Municipal Science
and Technology Commission (Z181100002218033), and
China Postdoctoral Science Foundation (212400211).
AUTHOR CONTRIBUTIONS
Xuran
Zhang:
Conceptualization;
investigation.
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Qianqian Gan: Investigation. Qing Ruan: Investigation.
Di Xiao: Investigation. JunBo Zhang: Conceptualiza-
tion; funding acquisition.
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are
available from the corresponding author upon reasonable
request.
ORCID
Xuran Zhang https://orcid.org/0000-0002-1873-936X
Junbo Zhang https://orcid.org/0000-0003-3549-6483
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SUPPORTING INFORMATION
Additional supporting information may be found online
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How to cite this article: Zhang X, Gan Q,
Ruan Q, Xiao D, Zhang J. Evaluation and
comparison of 99mTc-labeled D-glucosamine
derivatives with different 99mTc cores as potential
tumor imaging agents. Appl Organomet Chem.
2020;34:e6008. https://doi.org/10.1002/aoc.6008