Vol.3, No.11, 663-667 (201
doi:10.4236/health.2011.311111
C
opyright © 2011 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
1) Health
The comp arison of intravenous and lymphotropic routes
of 99mTc ciprofloxacin in experimental pulmonary
suppuration
Yuriy Lishmanov1, Svetlana Sazonova1*, Yevgeny Sokolovich2, Vladimir Chernov1
1Institute of Cardiology of the Siberian Branch of the Russian Academy of Medical Sciences, Tomsk, Russia;
*Corresponding Author:
2Siberian Medical University, Tomsk, Russia.
Received 4 May 2011; revised 20 June 2011; accepted 25 July 2011.
ABSTRACT
Intravenously injected “99mTc-ciprofloxacin” is
rapidly accumulated and washed from the sep-
tic focus. Lymphotropic injections provide tar-
geted and lo ng-las ting eff ect o f antibi otics. After
injection into the inte rspi nous ligament the dr ug
slowly enters the inflammation area (by-passing
the urinary organs and liver), where it is maxi-
mally accumulated only after 24 h, which allows
to reduce the number of injections and the total
dose of the antibio tic.
Keywords: Pulmonary Suppuration; Lymphotropic
Route; 99mTc Ciprofloxacin
1. INTRODUCTION
Acute suppurative lung diseases are one of the most
actual medical-social problems, because they are char-
acterized by massive organ injury and severe, life-
threatening clinical course. It is well-known, that lym-
phatic system plays an important role in this pathology
and is actively involved into protective reactions of im-
mune system and detoxification [1,2]. Since the resorp-
tion of tissue fluid in suppurative-inflammatory process
is attended with considerable enhance of endolymphatic
concentration of pathological microorganisms, the di-
rected increasing of antibiotic concentration in lymphatic
system may result in the therapeutic effectiveness
strengthening of such kind of drugs [2]. However, tradi-
tional routes of antibiotics are enabling to accumulate
these drugs in sufficient concentrations in blood [3]. In
this connection, Levin Yu.M. et al. [4] in 1986 proposed
“method of indirect endolymphatic therapy”. It is based
on using drugs (tripsin, chemotrypsin, et al.) which are
able to change lymphatic vessels permeability making
possible to increase drug delivery into lymph capillaries.
It was shown, that such kind of pharmacological inter-
vention not only increases lymphatic concentration of
antibiotics in 2 - 10 times, but also stimulates lymph out-
flow from organs [5].
Numerous methods of limfocorrection and limfosani-
tation, including limfostimulatory interspinal injections
suggested by M.S. Lubarsky [6] are now widely used in
practical medicine.
Nevertheless, the advantage of endolymphatic therapy
to intravenous route of administration of antibiotics is
not conclusive, because there is still no convincing data
on the dynamics of drug accumulation in the inflamma-
tory foci, as well as the pharmacokinetics and washout.
Recently, a new radiopharmaceutical - antibiotic cipro-
floxacin labeled with 99mТс, have been proposed for di-
agnoses of infective inflammation [7]. In our opinion, it
can be used in experimental studies to trace the dynamic
of antibiotic accumulation in the lung inflammatory foci
and to compare the effectiveness of intravenous and en-
dolymphatic routes of this medicine.
To compare the extent of 99mТс-ciprofloxacin accu-
mulation in the lung inflammation after intravenous or
endolymphatic route.
2. MATHERIALS AND METHODS
Experiments were carried out on 12 adult mongrel
dogs of both sexes, and kept before and after the ex-
periment in normal vivarium conditions. All experiments
were performed under general anesthesia. The main se-
ries of experiments were performed on 5 dogs, with pre-
liminarily modeled acute staphylococcal pneumonia
(method of L. A. Mamedov) [8].
To this purpose the suspension containing 1,000,000
microbial cells of Staphylococcus aureus was injected
into the lung tissue of animals at the level of VII-VIII
intercostal space on the right. The process of the in-
flammatory infiltrate formation was evaluated by clinical

Y. Lishmanov et al. / Health 3 (2011) 663-667
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and X-ray methods. In 5 days after experimental con-
tamination in a strictly aseptic conditions at the level of
Тh2-Th3, Тh3-Th4, Тh4-Th5 (places of the greatest repre-
sentation of superficial lymph collectors) dogs were in-
jected with prepared ex tempore drug mixture consisting
of 32 units lidazy, 4 mg dexamethasone, 100 mg, 10%
lidocaine, up to 6 ml of 40% glucose and 2 mg 200 - 300
MBq 99mТс-ciprofloxacin (Institute of Organic Synthesis,
Ural Branch of Russian Academy of Science). The ra-
diopharmaceutical, with radiochemical purity 95% was
synthesized in Tomsk Polytechnic University []. Regis-
tration of scintigraphic images was performed at 1, 2, 3,
4, and 24 hours post injection.
In 2 days after the first study 99mТс-ciprofloxacin
with the same drug mixture was injected to animals in-
travenously (into the small subcutaneous vein of the hind
limb). Tracing of the radiopharmaceutical’s distribution
was performed at 1, 2, 3, 4, and 24 hours post injection.
For control studies we used three groups of healthy
animals (3 dogs each), which initially were intrave-
nously injected with even drug complex, containing ra-
diopharmaceuticals with different chemical and biologi-
cal properties: for animals of the first group—99mTc-
pertechnetate (ТсО4Na), for the second—99mТс-radioac-
tive colloid, for the third—99mТс-ciprofloxacin. Two
days later the same radiopharmaceuticals were injected
by lymphotropic route with hereinabove method.
Registration of scintigraphic images in control groups
was performed at 1, 2, 3, 4 and 24 hours post injection.
At the time of the study, all dogs were located ventral
surface of the detector γ-camera so that the field of view
proved to the whole body.
Scintigraphic studies were carried out on the gamma
camera “Philips-Forte”. Pprocessing of scintigraphic data
was performed using a package “Jet Stream® Workspace
Release 2.5” (Philips) following by isolation of zones of
interested and making “time-activity” curves.
3. RESULTS AND DIS CUS SION
After 1 h after intravenous injection of 99mTc-cipro-
floxacin maximum of its accumulation was registered in
the kidney ( 30% of total activity) and bladder ( 60%
of total activity) that corresponds to the normal biodis-
tribution radiopharmaceutical [7].
The dynamics of accumulation of 99mTc-ciproflox-
acine in lungs is shown on Figure 1, which follows that
radioactivity in the inflammation foci reached its maxi-
mum after 2 hours (6.9% ± 0.3% of total) post injection
with further slow washing-out of the indicator. Concen-
tration of the drug throughout the experiment in the in-
tact lung tissue remained significantly lower than in the
area of damage (the index “inflammatory foci/lung tis-
sue” has averaged 0.7 ± 4.2) and after 2 hours did not
exceed 1.6% ± 0.2% of the total activity. By the end of
the experiment (24 hours), the radioactivity of lung tis-
sue in the zone of interest was not different from back-
ground values.
On scintigrams of animal’s chests obtained 2 hours
after the lymphotropic introduction (into the interspinous
ligament) of the radiofarmaceutical, the most intensive
(local) accumulation of the indicator was marked at the
site of antibiotic’s injection (Figure 2). This pattern per-
sisted throughout the study. In the perifocal area and in
Figure 1. The dynamics of accumulation of 99mTc-ciprofloxacine in lungs after intravenous injec-
tion. (1: radioactivity in the inflammation foci; 2: radioactivity in the intact tissue).

Y. Lishmanov et al. / Health 3 (2011) 663-667
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665665
Figure 2. The dynamics of accumulation of 99mTc-ciprofloxacine in lungs after the lymphotropic
injection. (1: site of injection; 2: inflammation foci; 3: lung root projection; 4: lung).
0.2% and 4.5% ± 0.4% of the total body radioactivity,
respectively.
On scintigrams obtained 24 hours after injection of the
indicator clearly visualized as increased radioactivity at
the site of injection, and the medium-intensity local ac-
cumulation of 99mTc-ciprofloxacin in the inflammation of
the right lung. Later on in concordance with radioactive
decay of technetium it was the gradually slow decreasing
of the rate of scintillation counting over the lung area,
and two days later the presence of the radiopharmaceu-
tical was not registered.
Distribution of “99mTc-pertechnetate” after its lym-
photropic injections to healthy dogs is shown in Figure
3(a). After 1 h post injection there was rapid redistribu-
tion of the radiopharmaceutical with a maximum accu-
mulation in the stomach (2.2% of total activity). In the
same period at the lung root projection the presence of
indicator was minimal, averaging 1.1% of the total ac-
tivity. Further 99mTc-pertechnetate washed out from the
injection site with a parallel increasing of its concentra-
tion in a stomach. After 4 hours, the drug distributed as
follows: 0.8% of the administered activity at the inject-
tion site, 1.4%—in the lung root projection, 3.2%—in
the stomach, the rest—are uniformly throughout the
body. After a day in the thorax activity was not recorded.
The distribution of 99mТс-radioactive colloid after in-
troduction into the interspinous ligament was as follows:
at 1 h post injection the main part of the drug remained
at the injection site (96.3%), at 3 hours—a small activity
(4.6% of the total), appeared in liver, at the same time in
the lung root projection accumulation of radiopharma-
ceutical was not observed (Fi gure 3(b)).
Figure 3(a) shows the pharmacokinetics of 99mTc-
ciprofloxacin after lymphotropic introduction to healthy
dogs. At the first stage of the experiment 16% of antibi-
otics remained in the injection site, following by its
gradual washing-out from this area and increasing in a
lung root. After 4 hours at chest slices, along with the
area of administration, clearly visualized fixation of the
radiopharmaceutical in the lung root projection (7.4% of
the total), which remained high (7.1%) also at 24 hours.
In the same time radioactivity at the injection site de-
clined to 13.2%. In the lung tissue at all stages of the
study activity of 99mTc-ciprofloxacin has remained low
and averaged 3.5%.
After intravenous injection each of three radiophar-
maceuticals accumulated in dog’s organs according to
the normal physiologic distribution of these indicators
[9].
Thus, the results of experiments showed that the in-
travenous route of antibiotic ensures its rapid accumula-
tion and washing-out from a septic focus. Such use of
the drug can be necessary when an urgent creation of a
high concentration of drug in the area of bacterial lesions
is needed. On the other hand, the rapid washing-out of
the drug from the target organ determines the need of
frequent repeated injections, the amount of which de-
pends on the choice of drug, its chemical and biological
properties. In addition, intravenous injection, as is
known, is accompanied by binding of antibiotics with
blood proteins, making it necessary to use sufficiently
high concentrations of these drugs to achieve therapeutic
effect, which is unfavorable for the organism as a whole.
Lymphotropic route of administration provides, in
accordance with our data, targeted and sustained action
of antibiotic. Thus, “99mTc-ciprofloxacin” after injection

Y. Lishmanov et al. / Health 3 (2011) 663-667
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666
(a)
(b)
(c)
Figure 3. Distribution of different radio pharmaceuticals after
limfotropic injection to healthy dogs (% of total activity). (a)
“99mTc-pertechnetate”; (b) “99mTc-radioactive colloid”; (c)
“99mTc-ciprofloxacin”; 1: injection site; 2: lung root projection;
3: stomach; 4: liver; 5: lung.
into the interspinous ligament, avoiding urinary tract and
liver, slowly delivered to the area of inflammation, where
reaches a maximum only after 24 hours. This fact sug-
gests the possibility of reducing the number of inject-
tions to 1 in 24 - 36 hours, as well as reducing the total
dose and the toxic effects of the drug. When there is a
need for rapid achievement of high concentrations of
antibiotic in the inflammatory foci and preservation of
prolonged antimicrobial effect, in our opinion, the com-
bination of both methods of administration is possible.
This intends a treatment regimen that includes initial
intravenous injection of antibiotics with subsequent
transition to lymphotropic injections until the end of
treatment.
Results of control studies have shown the absence of
local accumulation of “99mTc-ciprofloxacin” in lung tis-
sue of healthy animals, which once again confirms the
ability of radiopharmaceutical to accumulate selectively
in sites of tissue damage. Significant dependence of ab-
sorption rates of radiopharmaceuticals from the injection
site to lymphatic system on theirs physicochemical
properties suggests that the frequency of lymphotropic
injections will depend on the characteristics of the se-
lected drug. For example, colloidal radiopharmaceutical,
which has the largest molecular weight, within two days
remained in the injection site and didn’t enter the lym-
phatic and circulatory systems, while “99mTc, pertech-
netate” the most rapidly absorbed into the blood.
In conclusion, it should be noted that this study con-
firms the possibility of antibacterial agent’s delivery into
the inflammatory foci by interspinous injection and as a
result reduction of daily and course dose of antibiotics.
However, in our opinion, this question requires further
experimental biochemical, and clinical researches.
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