Preclinical and clinical studies of bone marrow uptake of fluorine-1-fluorodeoxyglucose with or without granulocyte colony-stimulating factor during chemotherapy.
OBJECTIVE
To evaluate the effect of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on bone marrow glucose metabolism in rodents and in patients, as assessed by 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) uptake measured directly or by positron-emission tomography (PET) scanning.


METHODS
Groups of three rats received either daily saline, G-CSF, or GM-CSF injections for 7 days. After treatment, FDG was injected and F-18 activities in tissues measured 1 hour later. Twenty-two breast cancer patients treated with multiagent chemotherapy were sequentially studied with PET. Eleven patients received G-CSF therapy as an adjunct to chemotherapy, while 11 received chemotherapy only. The standardized uptake value-lean (SUL) of bone marrow FDG uptake was measured and compared.


RESULTS
In rats, bone marrow F-18 activity was significantly higher in both CSF groups than in the saline group (G-CSF, 0.44 +/- 0.08; GM-CSF, 0.33 +/- 0.02; saline, 0.18 +/- 0.02% injected dose [ID]/g x kg; P < .05), but the other normal tissues had comparable biodistributions to controls. In breast cancer patients, the FDG uptake of bone marrow did not change with chemotherapy alone; however, marrow uptake was increased after treatment with G-CSF. The dose of G-CSF and duration of treatment were correlated with the extent of increase in FDG uptake. The SUL of bone marrow was as follows: baseline, 1.56 +/- 0.23; after one cycle, 3.13 +/- 1.40 (P < .01); after two cycles, 2.22 +/- 0.85 (P < .05); and after three cycles, 2.14 +/- 0.79 (P < .05), respectively. Although the FDG uptake of bone marrow declined after G-CSF treatment was completed, it was higher than the baseline level for up to 4 weeks postcompletion of G-CSF and the elevated marrow FDG uptake was sustained longer than the period of blood neutrophil count elevation.


CONCLUSIONS
Substantial increases in bone marrow FDG uptake are rapidly induced by CSF treatments and should not be misinterpreted as diffuse bone marrow metastases.
Sugawara
Y
Y
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0028, USA.
Fisher
S J
SJ
Zasadny
K R
KR
Kison
P V
PV
Baker
L H
LH
Wahl
R L
RL
D000328:Adult; D000368:Aged; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D005947:Glucose / Q000378:metabolism*; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014055:Tomography, Emission-Computed
D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D005947:Glucose