RAMB - DEZEMBRO

role

regulatory

cells

interleukin

-10

and

vivo

scintigraphy

autoimmune

and

idiopathic

diseases

– T

herapeutic

perspectives

and

prognosis

ssoc

ras

2017; 63(12):1090-1099

1097

other hand, may promote an early diagnosis of inflamma-

tory processes by monitoring the early stages of inflam-

mation. Thus, radioisotope scintigraphy is expected to

contribute to the diagnosis of RA by monitoring func-

tional and physiological changes at the inflamed site

before anatomical structural changes consequent to RA

can become apparent.

Positron-emitting fluoride-18-labeled deoxy-glucose

(FDG) is a radiopharmaceutical used in positron emission

(PET) scintigraphy. The compound accumulates in the

inflammatory site, given the high local metabolism. The

high supply of leukocytes in the inflamed site leads to

increased glucose consumption.

However, due to the

high cost of production of this 110-minute half-life radio-

pharmaceutical, together with the cost of PET imaging, it

is currently impracticable to perform systematic clinical

studies of RA using this technique. Cost reduction or new

methods and radiopharmaceuticals should be produced

to enable scintigraphy of RA.

The use of radiolabeled

ex-vivo leukocytes is attractive; however, they involve dif-

ficult management with high control of sterility and apy-

rogenicity.

Although leukocyte scintigraphy radiolabeled

with

111

In and

99m

Tc is a gold standard for the diagnosis

of inflammation, the process of marking autologous leu-

kocytes with

99m

Tc-HMPAO demands manipulation of

blood samples in aseptic facilities with the reintroduction

of these samples into the patient.

Obviously, there is the

inherent risk of contamination, during manipulation of

PBMC cells and isolation and labeling of leukocytes.

A recent patent PI0904754-9, developed by the re-

search group coordinated by the author, has shown that

Tc-99m-labeled thio-sugar analogues of glucose are effi-

cient in detecting inflammations.

Previous synthesis

studies had been successfully performed using 5-thio-D-

glucose; however, due to cost issues, there was a need to

replace the thio-sugar molecule.

The importance of

thio-sugars in inflammations was demonstrated in the

temporomandibular joint (TMJ) of rats.

The patent

involves 5-thio-glucose and 1-beta-thio-D-glucose labeled

with Tc-99m.

The results show significant differences

in the uptake of

99m

Tc-1-TG in the inflamed TM joint

compared to the control, with high renal excretion.

Tc-99m-labeled glucose analogs may become radiophar-

maceuticals important for detection in the monitoring

of inflammations such as AR due to the low cost and high

technological feasibility. However, despite the murine

investigations, there is still a need for clinical investiga-

tions demonstrating its efficiency in the early detection

of RA and the degree of disease involvement in humans

before and after immunological treatment.

Research on the synthesis and characterization of sug-

ars with heavy metals has advanced. Recently, Dalmazio and

Campos

demonstrated by mass spectrometry the viability

of direct labeling of sugar polymolecules with Sm, Gd, B, Li,

Tc, Sm, Ho, Eu, and other elements. These metal-sugar com-

plexes make it possible to define several tracers for differ-

ent modalities of medical imaging tests. These studies lack

in vivo experimentation, but already offer a promising per-

spective in the monitoring of autoimmune diseases.

IL-1 and IL-6 interleukins play a crucial role in RA

and osteoarthritis in the early processes of cartilage break-

down and destruction.

A significant increase of IL-6 in

patients with osteoarthritis was identified by Kaneyama

et al.

In 2014, in turn, Sukedai et al.

report the relation

between TNF-

and cartilage degeneration. These authors

show that IL-8 is closely involved with the acute phase of

the inflammatory process. Thus, interleukins, such as

IL-1, IL-6, IL-8, are proteins with which in vivo monitor-

ing may lead to differential diagnosis of RAs.

Radiolabeled sugars serve the monitoring of inflam-

mation induced by autoimmune diseases; however, they

are not specific. It is worth saying that the interleukins

themselves have high potential for radiolabeling. Rennen

et al.

61,69

performed the labeling of IL-8 with Tc-99mmak-

ing it possible to diagnose inflammation through radiola-

beled interleukins.

Thus, we conclude that inflammatory

cytokines are potential markers to aid in the diagnosis and

prognosis of anti- and pro-inflammatory and degenerative

changes in situ, monitoring the course of the disease. Ra-

diolabeled cytokines, together with high metabolism label-

ing radiopharmaceuticals, represent a promising class of

compounds for the evaluation of autoimmune diseases,

since these proteins play an important role in inducing

and maintaining the disease process.

onclusion

The present review addressed cellular markers whose anal-

ysis and modulation may be useful in the treatment of

autoimmune and idiopathic diseases, as well as in the prog-

nostic monitoring of diseases. It has been noted that the

ex-vivomonitoring andmanipulation of interleukin IL-10

is relevant for treatment, and that thio-sugars, monossacha-

rides, polysaccharides and radiolabeled interleukins are

tools for in vivo monitoring of autoimmune and idio-

pathic diseases. Future consolidation of scintigraphic

methods can help monitor the progression of such dis-

eases. Advances in research on modulation and generation

of radioactive drugs involving cell markers for diagnosis

and therapy may bring benefits to patients with autoim-

mune diseases.