99mTc-Sestamibi scanning with SDZ PSC 833 as a functional detection method for resistance modulation in patients with solid tumours.
BACKGROUND
Our aim was to determine the value of 99mTc-Sestamibi scanning as functional detection method of P-glycoprotein (Pgp) blockade by PSC 833 in solid tumour patients.


METHODS
Day 1 and day 4 after 2,200 mg orally administered PSC 833 the tumour area was scanned after intravenous (i.v.) administration of 400 MBq 99mTc-Sestamibi. In tumours with net 99mTc-Sestamibi uptake and in the hepatic region K-efflux was determined. Whole blood was analyzed for 99mTc-Sestamibi, and PSC 833 levels.


RESULTS
Fourteen patients were included. In the only Pgp-positive tumour with positive 99mTc-Sestamibi scanning K-efflux of 99mTc-Sestamibi decreased significantly after PSC 833 intake. A net inhibition of liver efflux of Sestamibi after PSC 833 intake was observed in all evaluable patients. PSC 833 blood levels were all above 2 mg/L during scanning; 99mTc-Sestamibi blood levels post versus pre PSC 833 were unchanged.


CONCLUSIONS
PSC 833 induced modulation of K-efflux of 99mTc-Sestamibi in a Pgp positive tumour and in all patients in the liver.
Bakker
M
M
Department of Pulmonary Disease, University Hospital Groningen, The Netherlands.
van der Graaf
W T
WT
Piers
D A
DA
Franssen
E J
EJ
Groen
H J
HJ
Smit
E F
EF
Kool
W
W
Hollema
H
H
Müller
E A
EA
De Vries
E G
EG
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000378:metabolism; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000000981:diagnostic imaging; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging; D002813:Chondrosarcoma / Q000000981:diagnostic imaging; D003524:Cyclosporins / Q000008:administration & dosage / Q000493:pharmacokinetics; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging; D008175:Lung Neoplasms / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D012509:Sarcoma / Q000000981:diagnostic imaging; D017256:Technetium Tc 99m Sestamibi
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003524:Cyclosporins; D019275:Radiopharmaceuticals; D017256:Technetium Tc 99m Sestamibi; C070272:valspodar