In vivo tracking of dendritic cells in patients with multiple myeloma.
Dendritic cell (DC) immunotherapy is being actively studied in multiple myeloma (MM). We aimed to use positron emission tomography or single positron emission tomography to determine the in vivo distribution of monocyte-derived nonmatured DC or matured DC (mDC) administered to patients with MM. Eligible patients had stable or slowly progressive MM and elevated serum MUC-1 or MUC-1 expression on marrow plasma cells. DCs were derived from granulocyte-macrophage colony-stimulating factor+ interleukin-13 stimulated autologous monocytes, pulsed with mannan-MUC1 fusion protein, and matured by FMKp and interferon-gamma. Before injection, DCs were labeled with either 18fluorine-fluorodeoxyglucose, 111indium-oxine or 64copper-pyruvaldehyde-bis-N-4-methylthiosemicarbazone. Labeled DCs were given either as a single intravenous dose or by concurrent subcutaneous (SC), intradermal (ID), and intranodal routes. 18Fluorine-fluorodeoxyglucose tracking was unsuccessful owing to high radiolabel efflux. 64Copper-pyruvaldehyde-bis-N-4-methylthiosemicarbazone-labeled mDC (n=2 patients) demonstrated tracking to regional nodes but quantitation was also limited owing to cellular efflux. 111Indium-oxine, however, gave reproducible tracking of both nmDc and mDC (n=6) to regional lymph node after either SC or ID administration, with mDC revealing superior migration to regional lymph node. SC and ID routes produced similar levels of DC migration.
Prince
H Miles
HM
Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, VIC 3002, Australia. miles.prince@petermac.org
Wall
Dominic M
DM
Ritchie
David
D
Honemann
Dirk
D
Harrrison
Simon
S
Quach
Hang
H
Thompson
Mick
M
Hicks
Rodney
R
Lau
Eddie
E
Davison
Jill
J
Loudovaris
Maureen
M
Moloney
Jude
J
Loveland
Bruce
B
Bartholeyns
Jacques
J
Katsifis
Andrew
A
Mileshkin
Linda
L
D000368:Aged; D000906:Antibodies / Q000097:blood / Q000276:immunology; D000942:Antigens, Bacterial / Q000494:pharmacology; D015703:Antigens, CD / Q000032:analysis; D002465:Cell Movement / Q000276:immunology*; D016207:Cytokines / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000473:pathology / Q000637:transplantation*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000737:chemistry; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007711:Klebsiella pneumoniae / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood / Q000276:immunology; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D009942:Organometallic Compounds / Q000737:chemistry; D015125:Oxyquinoline / Q000031:analogs & derivatives / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000737:chemistry; D013154:Spleen / Q000473:pathology; D013882:Thiosemicarbazones / Q000737:chemistry; D014055:Tomography, Emission-Computed / Q000379:methods
D000906:Antibodies; D000942:Antigens, Bacterial; D015703:Antigens, CD; D016207:Cytokines; C060192:MUC1 protein, human; D018396:Mucin-1; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D013882:Thiosemicarbazones; D019788:Fluorodeoxyglucose F18; C032950:indium oxine; C052629:copper pyruvaldehyde bis(N(4)-methylthiosemicarbazone) complex; D015125:Oxyquinoline; D007371:Interferon-gamma