TY - JOUR
T1 - Identifying CD381 cells in patients with multiple myeloma
T2 - First-in-human imaging using copper-64–labeled daratumumab
AU - Krishnan, Amrita
AU - Adhikarla, Vikram
AU - Poku, Erasmus K.
AU - Palmer, Joycelynne
AU - Chaudhry, Ammar
AU - Biglang-Awa, Van Eric
AU - Bowles, Nicole
AU - Nathwani, Nitya
AU - Rosenzweig, Michael
AU - Sahebi, Firoozeh
AU - Karanes, Chatchada
AU - Simpson, Jennifer
AU - Sanchez, James F.
AU - Yamauchi, Dave
AU - Parayno, Maria
AU - Chowdhury, Arnab
AU - Caserta, Enrico
AU - Marcucci, Guido
AU - Rockne, Russell
AU - Wu, Anna M.
AU - Wong, Jeffrey
AU - Forman, Stephen J.
AU - Colcher, David
AU - Yazaki, Paul
AU - Shively, John
AU - Pichiorri, Flavia
N1 - Publisher Copyright:
© 2020 by The American Society of Hematology
PY - 2020/10/23
Y1 - 2020/10/23
N2 - 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/ CT) is one of the most widely used imaging techniques to detect multiple myeloma (MM). Intracellular FDG uptake depicts in vivo metabolic activity, which can be seen in both malignant and nonmalignant cells, resulting in limited sensitivity and specificity. Our group showed preclinically that tracing MM dissemination using a CD38-directed human antibody, daratumumab, that is radioconjugated with 64Cu via the chelator DOTA (64Cu-daratumumab), led to improved sensitivity and specificity over that of FDG. Here, we report the results of a phase 1 trial designed to (1) assess the safety and feasibility of 64Cu-daratumumab PET/CT and (2) preliminarily evaluate and characterize the ability of 64Cu-daratumumab to accurately detect or exclude MM lesions. A total of 12 daratumumab-naive patients were imaged. Prior to the injection of 15 mCi/5 mg of 64Cu-daratumumab, patients were treated with 0 (n 5 3), 10 (n 5 3), 45 (n 5 3), or 95 mg (n 5 3) of unlabeled daratumumab to assess its effect on image quality. No significant adverse events were observed from either unlabeled daratumumab or 64Cu-daratumumab. Of the dose levels tested, 45 mg unlabeled daratumumab was the most optimal in terms of removing background signal without saturating target sites. 64Cu-daratumumab PET/CT provided safe whole-body imaging of MM. A trial comparing the sensitivity and specificity of 64Cu-daratumumab PET/CT with that of FDG PET/CT is planned. This trial was registered at www.clinicaltrials.gov as #NCT03311828.
AB - 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/ CT) is one of the most widely used imaging techniques to detect multiple myeloma (MM). Intracellular FDG uptake depicts in vivo metabolic activity, which can be seen in both malignant and nonmalignant cells, resulting in limited sensitivity and specificity. Our group showed preclinically that tracing MM dissemination using a CD38-directed human antibody, daratumumab, that is radioconjugated with 64Cu via the chelator DOTA (64Cu-daratumumab), led to improved sensitivity and specificity over that of FDG. Here, we report the results of a phase 1 trial designed to (1) assess the safety and feasibility of 64Cu-daratumumab PET/CT and (2) preliminarily evaluate and characterize the ability of 64Cu-daratumumab to accurately detect or exclude MM lesions. A total of 12 daratumumab-naive patients were imaged. Prior to the injection of 15 mCi/5 mg of 64Cu-daratumumab, patients were treated with 0 (n 5 3), 10 (n 5 3), 45 (n 5 3), or 95 mg (n 5 3) of unlabeled daratumumab to assess its effect on image quality. No significant adverse events were observed from either unlabeled daratumumab or 64Cu-daratumumab. Of the dose levels tested, 45 mg unlabeled daratumumab was the most optimal in terms of removing background signal without saturating target sites. 64Cu-daratumumab PET/CT provided safe whole-body imaging of MM. A trial comparing the sensitivity and specificity of 64Cu-daratumumab PET/CT with that of FDG PET/CT is planned. This trial was registered at www.clinicaltrials.gov as #NCT03311828.
UR - http://www.scopus.com/inward/record.url?scp=85096227784&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85096227784&partnerID=8YFLogxK
U2 - 10.1182/BLOODADVANCES.2020002603
DO - 10.1182/BLOODADVANCES.2020002603
M3 - Article
C2 - 33095874
AN - SCOPUS:85096227784
SN - 2473-9529
VL - 4
SP - 5194
EP - 5202
JO - Blood Advances
JF - Blood Advances
IS - 20
ER -