European Journal of Nuclear Medicine Vol. 28, No. 9, September 2001
Abstract. The occurrence of multidrug resistance (MDR),
which is in part due to the overexpression of P-glycopro-
tein (Pgp), is a major problem in neoadjuvant therapy of
malignant musculoskeletal tumours. The aim of this
study was to investigate the role of technetium-99m
hexakis-2-methoxyisobutylisonitrile (
99m
Tc-MIBI) scin-
tigraphy for functional imaging of the MDR1 phenotype
in patients with musculoskeletal sarcomas. We aimed to
compare
99m
Tc-MIBI uptake and washout kinetics with
the expression of Pgp and with chemotherapy response.
Twenty-five patients (16 males and 9 females, aged be-
tween 8 and 65 years) with malignant musculoskeletal
tumours were studied. After injection of 555–740 MBq
99m
Tc-MIBI, dynamic flow images of the involved area
were obtained for 3 min, and planar images were ac-
quired at 10 min and 1 h. From the dynamic images, a
tumour perfusion index (TPI) was obtained using Patlak-
Rutland analysis. Tumour to background (T/B) ratios of
both early and delayed images and percent wash-out rate
(WR%) of
99m
Tc-MIBI were calculated. Immunohisto-
chemical analysis of Pgp was performed on biopsy spec-
imens and the degree of expression was graded accord-
ing to a semiquantitative scoring system, from 0 to 6.
After neoadjuvant therapy, tumour response was as-
sessed by examining the ratio of viable cells and by de-
tecting percent necrosis. Scintigraphic results were com-
pared with Pgp status and therapy response. Irrespective
of the Pgp status, all patients showed significant perfu-
sion and
99m
Tc-MIBI uptake in early images. There was
not a significant correlation between T/B ratios of early
and delayed images and Pgp expression. We observed a
positive correlation between WR% and Pgp status
(r=0.61, P<0.01), and the wash-out rate of
99m
Tc-MIBI
was significantly higher in patients with high Pgp ex-
pression than in those with a low Pgp score (33%±9% vs
17%±9%). Therapy response was determined in 21 of
25 patients, and in only 5 of 21 cases was the percent ne-
crosis more than 90%. Neither Pgp expression rate nor
WR% was found to show a significant correlation with
percent necrosis in the bulk tumour specimens. In con-
clusion, the initial uptake of
99m
Tc-MIBI in bone and soft
tissue sarcomas did not correlate with Pgp expression. A
relationship was found between the wash-out rate of
99m
Tc-MIBI and the Pgp score, with a significant differ-
ence in WR% being observed between patients with high
and patients with low Pgp expression.
Keywords: Technetium-99m hexakis-2-methoxyisobutyl-
isonitrile – P-glycoprotein – Bone sarcoma – Soft tissue
sarcoma – Multidrug resistance
Eur J Nucl Med (2001) 28:1341–1350
DOI 10.1007/s002590100588
Introduction
The survival rate among patients with musculoskeletal
sarcomas is not encouraging despite the use of various
combinations of chemotherapy agents in conjunction
This work was presented in part at the annual meeting of EANM,
October 1999, in Barcelona, Spain.
Zeynep Burak (
✉
)
Department of Nuclear Medicine, Ege University Medical Faculty,
Bornova, 35100 I
.
zmir, Turkey
e-mail: zburak@egenet.com.tr
Fax: +90-232-3422142
Original article
The role of
99m
Tc-MIBI scintigraphy in the assessment
of MDR1 overexpression in patients
with musculoskeletal sarcomas:
comparison with therapy response
Zeynep Burak
1
, Özden Ersoy
2
, Jean-Luc Moretti
3
, Rüya Erinç
1
, Zehra Özcan
1
, Aysegül Dirlik
1
, Dündar Sabah
4
,
Gülçin Basdemir
2
1
Department of Nuclear Medicine, Ege University Medical Faculty, Bornova, 35100 I
.
zmir, Turkey
2
Department of Pathology, Ege University Medical Faculty, I
.
zmir, Turkey
3
Service de Médecine Nucléaire et Biophysique, Hôpital Avicenne, CHU Bobigny, Université Paris XIII, France
4
Department of Orthopaedics, Ege University Medical Faculty, I
.
zmir, Turkey
Received 5 February and in revised form 30 May 2001 / Published online: 10 July 2001
© Springer-Verlag 2001