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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5382_Библиотеки_им_академика_М_И_Перельмана.pdf
The 7α position (E-7) of 3,17β-estradiol, known to tolerate modications, was deriva-
tized to synthesize a series of ligands, a thiol (S-E7), an isocyanide (CN-E7), a dithioether
(SS-E7), as well as tridentate SSO (SSO-E7) and SNO (SNO-E7) chelators, in order to
employ dierent Re/
99m
Tc-chelate strategies. The “3+1” oxorhenium complexes ReOSSS/S-E7, ReO-SOS/S-E7, and ReO-SN(Me)S/S-E7 were synthesized, where a higher
anity of RBA=45% was observed for ReO-SN(Me)S/S-E7 and a lower binding anity
(RBA=15%) for the “4+1” complex Re-NS
Re(CO)
respectively[291, 296]. The [
(SSO-E7), and Re(CO)3(SNO-E7) complexes exhibited RBA=15%, 36%, and 27%,
3
94m
Tc][Tc(CO)3(SNO-E7)] analogue was evaluated in rats, but
/CN-E7. The organometallic Re(CO)3(SS-E7),
3
target-specic uptake in vivo was not observed.
The DPA tridentate chelator was conjugated to the 16α-position of estradiol by linkers of
varying length, and the respective Re(CO)
(DPA-Estradiol-16) complexes were prepared, with
3
the hexyl linker derivative exhibiting highest ERα anity (RBA=25.7%) among them[297]. In
a recent eort, 3-aminoethyl estradiol was conjugated to the DTPA chelator and labelled with
99m
Tc. The tracer was studied in vivo in estrogen and nonestrogen receptor-expressing tumor
cell lines, where signicantly higher uptake was observed in MCF-7 (ER+) tumors (6.06 ± 0.38
%ID/g) than by MDA-MB-231 (ER-) tumors (1.57 ± 0.28 %ID/g) at four hours p.i.[298].
Another class of ER imaging agents was designed based on tamoxifen, where one of
the three phenyl groups of tamoxifen (in particular, the β ring) was replaced by the Retricarbonyl-cyclopentadienyl moiety, leading to a mixture of isomers Z + E, which maintained a good binding anity for ERα and ER antagonist activity, with the highest anity
for an isolated Z isomer (RBA =28% at 0 °C) (Figure12.19)[299, 300]. Furthermore, new
cyclopentadienyl rhenium tricarbonyl complexes that contain two or three aryl moieties
as substituents of the cyclopentadiene have been developed, which have exhibited ER
binding with RBA values up to 23% (Figure12.19)[301]. Novel C-ring substituted rhenium cyclopentadienyl analogues of cyclofenil, a nonsteroidal compound known to bind
the ER, were also prepared, with low ER binding[302]. Also, a series of mono and diaryl
rhenium(I)-carborane derivatives were prepared using microwave heating, which exhibited an anity for the two isoforms of the ER[38].
12.8.12 Cobalamin Receptor Imaging Agents
The development of
imaging. Various proteins recognize and transport cobalamin throughout the body. It is
known that certain cancer cells show an increased extracellular density of receptors that
bind to cobalamin, and although cobalamin labelled with radioactive cobalt isotopes has
been explored for cancer imaging, high uptake in the liver, kidney, and spleen, among
other tissues, was observed. A few eorts reported the development of
via the [
99m
Tc]technetium-tricarbonyl approach[303, 304]. First, N(τ)-histidine derivatives
were conjugated to the b-acid, c-acid, and d-acid of cyanocobalamin via amide formation.
The analogous tracers [
tested in B16-F10 melanoma-bearing mice. The tumor uptake ranged from 4.4 ± 0.9% ID/g
to 9.2 ± 2.0% ID/g, while all tracers exhibited signicant kidney and liver uptake, similar
99m
Tc-cobalamin (Vitamin B12) may prove to be useful in oncological
99m
Tc-cobalamin
99m
Tc][Tc(CO)3(His-B12)] were prepared in high yield and were
Chapter 12:
99m
Tc Radiopharmaceutical Chemistry 415
to the respective values of [57Co]-cyanocobalamin. The b-acid derivative of B12 among
OC
OC
2
these tracers exhibited an improved excretion prole with a lower percentage of radioactivity in the kidneys and the liver[305]. Another derivative of cyanocobalamin b-acid
conjugated to S-derivatized cysteine was also prepared and labelled with
the tracer [
99m
Tc]Tc(CO)3(S-cys-b-B12). In B16-F10-bearing mice, it exhibited tumor uptake
99m
Tc to obtain
of 8.1 ± 0.6% ID/g at four hours p.i., while high liver and kidney uptake were observed
as well[19]. The tridentate chelator PAMA was conjugated via C2–C6 spacers to cobalamin b-acid, and these derivatives were labelled to form the respective tracers [
[Tc(CO)
(PAMA-C
3
-b-B12)] (Figure12.20). These tracers were evaluated for their interac-
2–6
99m
Tc]
tion with various cobalamin transporters. It was shown that in the short-chain derivatives,
their ability to interact with the transport protein transcobalamin II was abolished as well
as their mediated uptake in normal tissue; therefore, these tracers might display preferential accumulation in cancer tissue. In particular, the derivative with a butyl spacer exhibited
the highest tumor uptake in B16-F10-bearing mice, of approximately 8% ID/g at 24 hours
p.i., and low kidney and liver uptake[306]. This agent was also evaluated in a phase I pilot
study in human cancer patients, where it was shown that tumor visualization was possible
after pretreatment with cobalamin to saturate the circulating haptocorrin[307].
12.9 SENTINEL LYMPH NODE IMAGING AGENTS
Sentinel lymph node (SNL) imaging is helpful in identifying the rst lymph node to receive
lymphatic ow from the primary tumor site and is also useful intraoperatively. The
labelled lymph node imaging agents are based on macromolecules whose particulate
99m
Tc-
Figure 12.20
Structure of
a
derivative.
99m
Tc-B12
OC
N
O
O
Tc
N
H2NOC
416 Handbook of Radiopharmaceuticals
O
HN
H2NOC
N
N
CN
Co
N
N
O
HN
–
O
99m
[
Tc][Tc(CO)3(PAMA-C4-b-B12)]
OH
O
O
P
O
N
N
O
OH
CONH
CONH
2
CONH
2
properties allow for ecient drainage into the lymphatic system after intradermal or sub-
NH
Tilmanocept
cutaneous injection. Mannose-bound macromolecules (e.g. dextrans) provide selective
recognition via the mannose receptors of the reticuloendothelial system. A modied
dextran (Dx) bearing amino-terminal units was conjugated to multiple units of mannose
and MAG
3
as the
99m
Tc-chelator, and the nal macromolecule contained 3 MAG3 and 21
mannose units per dextran with a molecular weight of 19 389 g/mol and 5.5 nm diameter
size[308]. Also, DTPA-mannosyl-dextran was developed, which contained 8 mol DTPA
and 55 mol mannose per dextran with a molecular weight of 35 800 g/mol and 7.1 nm
diameter size[309]. A preliminary SNL-detection study employing footpad injections of
99m
[
Tc]Tc- MAG3-mannosyl-Dx and [
99m
to [
Tc]Tc-sulfur colloid (SC) as a standard radiopharmaceutical showed that both manno-
syl-Dxs had superior properties compared to
99m
Tc]Tc-DTPA-mannosyl-Dx (Figure12.21) in comparison
99m
Tc-SC and that [
99m
Tc]Tc- DTPA-ma nnosylDx exhibited faster injection-site clearance with a value of 45.7 ± 8.5% ID at three hours
p.i. and higher popliteal lymph-node extraction (knee sentinel lymph node for this model)
of 97.7 ± 2.0% ID at three hours p.i. in comparison to [
309]. The [
99m
Tc]Tc-DTPA-mannosyl-Dx underwent clinical trials and received approval for
99m
Tc]Tc- MAG3-mannosyl-Dx[308,
lymphoscintigraphy and intraoperative application (Lymphoseek,γ-Tilmanocept)[310].
99m
Tc-Tilmanocept was evaluated in human macrophages with high expression of the
C-type lectin mannose receptor (MR; CD206)[311]. Other mannosylated dextrans were
developed with tridentate chelators for [
99m
Tc]Tc-tricarbonyl labeling, which is known for
HO
HO
O
O
HO
HO
O
O
X
S
S
O
HN
NH
OH
HO
O
HO
HO
S
O
R =
HO
O O
O
X=12–20, Y=0–17, Z=3–8,
99m
R=[
N
N
O
Tc
O
Tc]Tc-DTPA:
O
99m
Figure 12.21 Structures of
O
Y
HO
O
O
Z
OHO
S
NH
2
NHR
O
N
N
or
O
Tc-
99m
Tc-labelled SNL imaging agents.
N
N
OC
X=13, Y=9, Z=8,
99m
R=[
NH
Tc
CO
CO
Tc]Tc(CO)3(pz),
HO
HO
OC
OC
OC
O
O
6
HO
HO
O
O
OH
43
HO
O
O
24
OHO
S
Tc
N
H
2
O
O
S
HOOC
HN
OH
O
HO
O
HO
HO
+
2
99m
[
Tc]Tc(CO)3(DCM20)
S
Chapter 12:
99m
Tc Radiopharmaceutical Chemistry 417
its higher chemical stability compared to the [
99m
Tc]Tc-DTPA chelate. The pyrazolyl diamine
(pz) chelator was conjugated to mannosyl-Dx, and among the derivatives obtained with
varying chelator and mannose concentration, the one with 8 mol pz and 13 mol mannose
per dextran of 20 kDa weight and 7 nm size (Figure12.21) exhibited better in vitro stability
and in vivo distribution properties. Its popliteal extraction was 94.47 ± 2.47% at one hour
p.i., higher than that of [
99m
Tc]Tc-colloid with 78.8 ± 6.5% and comparable to that of Lymphoseek with 90.1 ± 10.7%[312]. A modied dextran, S-cysteinyl-mannosylated-Dx, was
also developed with 6 mol of S-cysteinyl chelator and 24 mol of mannose per dextran
(CDM20, Figure12.21), 22 kDa weight, and 6.5 nm diameter size. The preliminary biological
evaluation of
99m
Tc-CDM20 in mice revealed high popliteal lymph-node uptake of 9.2%
ID at 30 minutes p.i. and fast clearance from the injection site of 67% ID at 30 minutes
p.i.[313]. Further biological evaluation of
99m
Tc-CDM20 showed that there was specic
uptake in dendritic cells (that express the mannose receptors) in vivo at the injection site,
which could explain their slower drainage compared to [
glycoalbumin[314]. A similar [
99m
Tc]Tc(CO)3-S-cysteinyl-mannosylated-Dx with a molecular
125
I]radioiodinated mannosyl-neo-
weight of 30 kDa and 9 and 36 units of cysteine and mannose, respectively, was evaluated
in mice, exhibiting 91.05 ± 9.65% popliteal extraction and 46.35 ± 3.16% ID remaining at
the injection site at 60 minutes p.i.[315]. A similar tracer, [
dicysteine (DCCM) with composition of Dx-(NH
weight of 35.5 kDa, was developed. The probe
, mannose13,(Cys–Cys)25 and molecular
2)46
99m
Tc-DCCM was evaluated in vivo, and high
99m
Tc]Tc(CO)3-dextran-mannose-
popliteal extraction of 98% at 60 minutes p.i. was obtained[316]. Also, a mannose-dextran
derivative bearing isonitrile moieties (DCM30-iso) was developed and was used with the
tripodal chelator 2,2′2″-nitrilotris(ethanethiol) (NS
99m
plex [
Tc]Tc(NS3)((DCM30-iso). The tracer exhibited 76.4 ± 12.3% popliteal extraction at
) to form the “4+1” mixed-ligand com-
3
60 minutes p.i. and 79.8 ± 3.0% ID at the injection site in rats[317].
Using a similar approach, HYNIC-mannosyl-neoglycoalbumin (HYNIC-NMA) was
developed as well and was labelled with technetium-99m in the presence of tricine as coligand. In this work, the
99m
Tc-labelled non-mannosylated HSA and
99m
Tc-colloid were also
studied for comparison purposes. After subcutaneous injection of the tracers in mouse
footpad, [
levels in the popliteal lymph node than did [
as well as faster clearance from the injection site compared to
99m
Tc]Tc-(HYNIC-NMA)-tricine demonstrated signicantly higher radioactivity
99m
Tc]Tc-(HYNIC-HSA)-tricine and
99m
Tc-colloid[318]. Also,
99m
Tc-colloid,
partially reduced mannosyl-HSA was labelled with technetium-99m, and the respective
99m
tracer
its analogous non-mannosylated protein,
tion site compared to
Tc-mannosyl-HSA exhibited higher uptake in the popliteal node in comparison to
99m
Tc-HSA, and faster clearance from the injec-
99m
Tc-colloids[319].
IMAGING AGENTS
The gold standard for imaging acute inammation is considered to be the
99m
cytes (
autologous
418 Handbook of Radiopharmaceuticals
Tc-WBC), an inammation-specic imaging agent. The preparation of a patient’s
99m
Tc-WBC is complicated and risky; thus, the agents
99m
99m
Tc-Sulesomab
Tc-leuko-
(Leukoscan) and
NH
H2N
, L=tricine/EDDA
[
Tc]Tc-ciprofloxacin (
Tc-Infecton)
99m
Tc-Besilesomab (Scintimun) were introduced. The rst is a murine
antibody Fab fragment for the granulocyte surface non-specic cross-reacting antigen
NCA-90, and the second is a whole murine monoclonal antibody specic for the granulocyte surface NCA-95. The tracers bind to granulocytes located in the abscess as well as
to circulating granulocytes and are used for the diagnosis of osteomyelitis and diabetic
foot ulcers. Another radiolabelled antibody,
99m
Tc-Fanolesomab[320] (LeuTech or NeutroSpect), was introduced, which is a murine monoclonal antibody specic to CD-15 receptors on neutrophils for diagnosis of acute appendicitis; however, it was discontinued due
to severe cardiopulmonary side eects. Other macromolecular imaging agents include
99m
Tc-human-nonspecic IgG, entrapped in the area of inammation due to increased
vascular permeability, as well as the
99m
Tc-nanocolloid, extravasated via the capillary
basement membrane followed by phagocytosis from the granulocytes and macrophages;
however, these agents are not specic for inammation. None of these agents is specic
for infection.
In an eort to develop infection-specic agents, the
lone antibiotic [
99m
Tc]Tc-ciprooxacin (Infecton) (Figure12.22) was introduced into the
99m
Tc-labelled uoroquino-
clinic for the imaging of bacterial infections[321, 322]. Recent work on the structure of
2
H2N
HO
HN
NH
O
N
H
O
H
N
N
O
H
HN
NH
H2N
proposed structure of [
O
O
O
N
F
N
O
H
N
N
Lys
H
O
5
HN
HN
O
NH
Tc
OH
HO
99m
H
N
N
F
N
O
O
O
O
O
Tc
S
O
H
N
N
H
7
Arg
NH
Tc][Tc-UBI(29–41)
O
H
N
N
O
H
O
NH
2
OH
H
N
O
H2N
N
O
HN
HN
H
N
O
N
H
N
NH
HN
O
N
H
O
H
N
NH
99m
[
Tc]Tc-isoniazid-iminothiolane
HN
O
H
N
OH
O
NH
NH
2
O
S
Tc
S
S
N
N
L
L
99m
[
Tc]TcHYNIC-UBI
S
Tc
NH
NH
N
N
H
N
N
H
L
L
NH
H
N
NH-UBI
29-41
O
29-41
O
O
N
N
H
99m
Figure 12.22 Structures of
99m
99m
Tc-labelled infection imaging agents.
Chapter 12:
99m
Tc Radiopharmaceutical Chemistry 419
[99Tc]Tc-ciprooxacin indicated that it is an oxotechnetium(V) complex coordinated with
two ciprooxacin molecules that act as O,O bidentate chelator. Similar results were also
obtained with the analogous rhenium-ciprooxacin complex[323]. Although initially,
99m
[
Tc]Tc-ciprooxacin was considered an infection-specic agent, recent studies revealed
accumulation in sterile inammation as well[324]. In a study that involved the evaluation
of both [
99m
Tc]Tc-ciprooxacin and [
cically bacterial infections, the
99m
Tc]Tc-enrooxacin for their ability to detect spe-
99m
Tc-tracers did not demonstrate preferential binding
to living bacteria[325]. Using another approach, the uoroquinolones were derivatized
to the respective dithiocarbamate (DTC) and then labelled with nitrodotechnetium,
where in the case of noroxacin-dithiocarbamate (Nfx-DTC), the tracer [
DTC)
] exhibited uptake of 3.43 ± 0.53% ID/g in the infected abscess at four hours p.i.,
2
99m
Tc][Tc N(Nfx-
0.79 ± 0.28% ID/g in the inammation (turpentine), and high liver and lung uptake[326].
Fluoroquinolones as well as the dithiocarbamate-derivatized uoroquinolones were
also labelled with [
99m
Tc][Tc(CO)3]. The tracer [
99m
Tc][Tc(CO)3(Ciprooxacin)] was evaluated in an infection mouse model, where the ratio of infected/noninfected thigh was
found to be 3.87:1, while in comparison, it was 3.17:1 for [
99m
The
Tc-labelled ciprooxacin-dithiocarbamate (Cipro-DTC) tracers were evaluated in
99m
Tc]Tc-ciprooxacin[327].
infected animals in vivo, where the abscess uptake was found to be 3.93 ± 0.74% ID/g for
99m
[
Tc][Tc(CO)3(Cipro-DTC)], 3.21 ± 0.66 for [
99m
[
Tc]Tc-ciprooxacin at four hours p.i.[328].
A number of cephalosporin antibiotics have been labelled with
tracers, [
99m
Tc]Tc-ceftriaxone was evaluated in infection and inammation animal models,
99m
Tc][Tc N(Cipro - DTC)2], and 1.24 ± 0.06 for
99m
Tc, and of these
where the target-to-nontarget ratio was found to be 3.6 for infection and 1.5 for inammation at four hours p.i.. This tracer was also evaluated in human skeletal infections,
which exhibited a diagnostic accuracy of 83.3%, sensitivity and a specicity of 85.2% and
77.8%, respectively[329].
Antimicrobial peptides, such as the cationic human antimicrobial peptide ubiquicidin,
develop electrostatic interactions with negatively charged bacterial membranes, and
they have been evaluated in the development of infection-specic radiopharmaceuticals.
In particular, the
99m
Tc-labelled ubiquicidin fragment UBI 29-41 (Thr-Gly-Arg-Ala-Lys-Arg-
Arg-Met-Gln-Tyr-Asn-Arg-Arg) was found to exhibit high binding in gram-positive and
-negative bacteria in vitro. [
99m
Tc]Tc- UBI 29 - 41 (Figure12.22) shows very high radiochemical yield and stability[330, 331]. The coordination of technetium is postulated to involve
the amine nitrogens of lysine and arginine-7, according to theoretical calculations[332,
333]. It exhibited an average infection-to-inammation ratio of 2.08 ± 0.49, which was
superior compared to the respective [
67
Ga]Ga-citrate ratio of 1.14 ± 0.45[332]. Its bacterial uptake was decreased after pre-treatment of the unlabelled peptide. It exhibits
high renal clearance and low hepatobiliary uptake. Clinical trials have proven its ability
to detect infection in humans with high sensitivity, selectivity, and accuracy[334]. Furthermore, its binding is proportional to the bacterial number in the infection foci, and
therefore it may be suitable to monitor the ecacy and duration of treatment[335]. In
patients,
99m
Tc-UBI 29- 41 has been evaluated in musculoskeletal infections, diabetic foot,
and antibiotic treatment monitoring[335, 336]. Furthermore, attempts were made to
420 Handbook of Radiopharmaceuticals
develop [
99m
Tc]Tc- HYNIC-UBI(29 - 41 ) (Figure12.22), due to the fact the HYNIC is a wellaccepted chelator and could potentially improve the biodistribution and stability of the
tracer. The tracer [
99m
Tc]Tc-tricine-HYNIC-UBI(29-41) was suitable for detecting the infection in human patients; however, it exhibited slower blood clearance and similar uptake in
the abscess of infected animals in comparison to [
99m
Tc]Tc- UBI(29-41)[333, 337, 338].
The development of a fungal infection-specic imaging agent is also highly desir-
able, and for this purpose, the tracer [
99m
Tc]Tc-uconazole was prepared by direct
labeling. It was found to be excellent in vivo for the detection of Candida albicans (T/NT
ratio=3.6 ± 0.47), with low accumulation in bacterial infection (T/NT ratio=1.3 ± 0.04) and
sterile inammation (lipopolysaccharide: T/NT ratio=1.4 ± 0.1) in mice[339].
The antitubercular isoniazid (INH) was derivatized with 2-iminothiolane and labelled
99m
with
agent. The respective tracer [
Tc by the direct method in an eort to develop a tuberculosis-specic imaging
99m
Tc]Tc-INH-2IT (Figure12.22) showed promise for tuberculosis imaging in animals, where the lesions were imaged with abscess/muscle ratio
of 2:1 at 2 hours p.i. and 3.5:1 at 24 hours p.i.. Furthermore, this agent was evaluated in
human patients and was able to visualize TB lesions[340, 341]. Isoniazid and ethionamide
(ETH) were conjugated to the cyclopentadienyl (cp) chelator via ligand transfer from
the ferrocene analogue and were labelled with [
99m
[
Tc][Tc(CO)3(cp-INH/cp-ETH)] exhibited low uptake in BCG (bacillus Calmette-Guérin)
99m
Tc][Tc(CO)3]+. The respective tracers
bacterial infection and high liver uptake[342, 343].
12.11
99m
Tc
Technetium-99m emits, on average, four Auger electrons per decay, and due to this fact,
99m
Tc-complexes have been evaluated as radiotherapeutic agents for tumors. Auger electrons have a short range (nm); therefore, in order for the Auger-emitting agent to elicit
signicant DNA damage, it is required that it possess the ability to accumulate into the
nucleus. For this purpose, [
nuclear intercalators, such as pyrene[344, 345], anthracene[346, 347], acridine orange[348],
and doxorubicin[349], and were tested for their ability to enter the cellular nucleus, cause
double-strand breaks in circular DNA, and cause cell death. From these eorts, it was shown
that the [
99m
Tc]Tc-tricarbonyl-pyrene-NLS tracer conjugated to an NLS (nuclear localization
signal) peptide (Figure12.23) was able to induce cell death in B16 cells by the eect of the
Auger electrons emitted by
conjugated to anthracene (Figure12.23) were developed, and it was shown that some of
these complexes exhibited the ability to target the cell nucleus of B16 cells and induce
enhanced cell death by the eect of the technetium’s Auger electrons[346, 347]. The
99m
[
Tc]Tc-tricarbonyl-dpa-doxorubicin tracer (Figure12.23) induced cell death in murine can-
cers[349]. It should be pointed out that the uorescent Re-tricarbonyl analogues of these
99m
Tc-tracers were not always detected in the cell nucleus in vitro by uorescence micros-
copy, because quenching may occur upon intercalation with DNA[349].
99m
Tc]Tc-tricarbonyl complexes were conjugated to various
99m
Tc[344]. Similarly, a series of [
99m
Tc]Tc-tricarbonyl complexes
Chapter 12:
99m
Tc Radiopharmaceutical Chemistry 421
+
O
OH
HO
O
OH
NH
Tc
CO
N
CO
N
OC
99m
[
Tc][Tc(CO)3(N,N,N-pyrene-NLS)]
H
N
Figure 12.23 Structures of
12.12 CONCLUDING REMARKS
In the previous sections, the literature was reviewed based on the criteria of novelty,
established chemistry for the reported tracers, and evidence of biological activity
or clinical application. New
especially in the area of the [
imaging agents developed over the past two decades have shown promise in human
patients as, for example, in the detection of gastroenteropancreatic neuroendocrine
tumors and the sentinel lymph node. New
developed with advantages over the older radiopharmaceuticals. Many of the
labelled peptides developed are also very attractive, and they may be applied in the
clinic in the future. The technetium-99m tricarbonyl complexes were introduced more
than 20 years ago as a promising platform for radiopharmaceuticals. It is noteworthy
99m
that
clinical trials in phase 3 for prostate cancer imaging in North America. Remarkable
eorts were also made in the drug-design of new targeted
receptors and the beta-amyloid, for example, but also in the development of
labelled glucose derivatives, even though no clinically useful imaging agent has
yet emerged.
N
NLS
O
99m
[
Tc][Tc(CO)3(pz-anthracene)
99m
Tc-labelled DNA intercalators.
HN
N
OC
99m
Tc-labelling methods and chelators were developed,
99m
Tc][Tc(CO)3]+-complexes. A number of new
Tc
CO
NH
CO
H
O
OH
O
O
+
2
99m
[
Tc][Tc(CO)3(DPA-doxorubicin)]
99m
Tc myocardial and renal agents were
N
O
O
OH
N
Tc
N
99m
Tc-based
99m
N
CO
Tc-Trofolastat is the rst technetium-99m tricarbonyl agent currently under
99m
Tc-probes for estrogen
99m
CO
CO
+
Tc-
Tc-
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