BCC6-th, Berlin 2008

** 99m **Tc-MIBI elimination by a tumor and response to chemotherapy in locally advanced breast cancer patients.

_Portnoj S.M., Shiryaev S.V., Odjarova A.A., Anurova O.A.,  Laktionov K.P., Rjabchikov D.A. _

N.N.Blokhin Russian Cancer Research Center, Moscow, Russia.

Introduction. Effective chemotherapy can convert locally advanced breast cancer to operable form and give chance for survival. Ineffective induction therapy means incurability on the whole. Predicting of the chemotherapy effect may give possibility to select optimal kind of therapy.

** Aim.** To estimate predictive significance of 99m Tc-MIBI accumulation and elimination by tumor on the effectiveness of neoadjuvant chemotherapy in locally advanced breast cancer patients.

Materials and methods. Investigation of accumulation and elimination of 99m Tc-MIBI by tumor was performed in 45 breast cancer patients (stages: IIa – 1, IIb – 1, IIIa – 7, IIIb – 31, IIIc – 5 patients) before the beginning of chemotherapy (CAF, FAC, docetaxel, 3-6 cycles). 99m Tc-MIBI was introduced intravenously (555 MBq), with the following two-phase (in 15 min and in average 3 hours) static scintigraphy of a breast. Coefficient of relative accumulation (CRA) of 99m Tc-MIBI in tumors in 15 min after injection (CRA1), CRA after 3 hours (CRA2), and percent of elimination (PE) were calculated [PE=(CRA1- CRA2)x100/CRA1]. All patients were operated.  “No residual tumor” and “Microscopic residual tumor” were united as “pathological effect”. **   **

Results. Clinical effect was observed in 82% (complete effect – in 6, partial effect – in 31, stabilization – in 7, and progression – in 1 patient). Pathological effect was observed in 29% (no residual tumor – in 4, and microscopic residual tumor – in 9 cases). The levels of CRA1 and CRA2 did not influence on the frequency of clinical or pathological effects. In patients with high level of the PE pathological effect was not attained (see table). High level of the PE was reviewed more rarely (2p<0.05) in patients with ER- HER2neu- tumors (19%), than in patients with ER+ HER2neu- tumors (47%), and than in patients with HER2neu+ tumors (75%).

Table. PE level and frequency of clinical and pathological effects

PE level	Frequency of clinical effects in %	Frequency of pathological effects in %
Low (<21%)	87 (26/30)	43* (13/30)
High (>22%)	73 (11/15)	0* (0/15)

*- 2p<0.05

**Discussion. **The best characterized mechanism of multidrug resistance (MDR) in cancer involves the MDR1 efflux transporter P-glycoprotein. The gamma-emitting organotechnetium complex, hexakis(2-methoxyisobutylisonitrile)technetium ( 99m Tc-MIBI) was validated as a substrate for MDR1 P-glycoprotein (1) and as a substrate for the multidrug resistance-associated protein pump (2). Ciarmiello A, et al. demonstrated in locally advanced breast cancer patients, that a rapid tumor clearance of 99mTc-sestamibi may predict lack of tumor response to neoadjuvant chemotherapy. Del Vecchio S., et al. found that early uptake of 99m Tc-MIBI in breast carcinomas is affected by alterations of apoptotic pathway. High levels of Bcl-2 prevented accumulation of 99m Tc-MIBI in tumors (4).

In this paper we reproduce results of the Ciarmiello A, et al. (3): 1/3 of breast cancer patients had rapid 99m Tc-MIBI** **elimination by a tumor, and such patients had not pathological response after induction chemotherapy.

Conclusion. Our first results confirm the main hypothesis: rapid 99m Tc- MIBI elimination by a tumor predicts the low pathological response to chemotherapy. Detection of the high level of 99m Tc-MIBI PE by tumor can indicate that neoadjuvant target therapy may be more preferential, than chemotherapy.

References.

1. Piwnica-Worms D., Chiu M.L., Budding M., et al. Functional imaging of multidrug-resistant P-glycoprotein with an organotechnetium complex. //Cancer Res. 1993.-53.-5.- p.977-984.

2. Hendrikse N.H., Franssen E.J., van der Graaf W.T., et al. 99mTc-sestaMIBI is a substrate for P-glycoprotein and the multidrug resistance-associated protein. //Br J Cancer. 1998.-77.-3.-p.353-358.

3. Ciarmiello A., Del Vecchio S., Silvestro P., et al. Tumor clearance of technetium 99m-sestaMIBI as a predictor of response to neoadjuvant chemotherapy for locally advanced breast cancer. //J Clin Oncol. 1998.-16.-5.- p.1677-1683.

4. Del Vecchio S., Zannetti A., Aloj L., et al. Inhibition of early 99mTc-MIBI uptake by Bcl-2 anti-apoptotic protein overexpression in untreated breast carcinoma. // Eur J Nucl Med Mol Imaging. 2003.-30.-6.- p.879-887.