TY - JOUR
T1 - First-in-human imaging with 89Zr-Df-IAB2M Anti-PSMA minibody in patients with metastatic prostate cancer
T2 - Pharmacokinetics, biodistribution, dosimetry, and lesion uptake
AU - Pandit-Taskar, Neeta
AU - O'Donoghue, Joseph A.
AU - Ruan, Shutian
AU - Lyashchenko, Serge K.
AU - Carrasquillo, Jorge A.
AU - Heller, Glenn
AU - Martinez, Danny F.
AU - Cheal, Sarah M.
AU - Lewis, Jason S.
AU - Fleisher, Martin
AU - Keppler, Jennifer S.
AU - Reiter, Robert E.
AU - Wu, Anna M.
AU - Weber, Wolfgang A.
AU - Scher, Howard I.
AU - Larson, Steven M.
AU - Morris, Michael J.
N1 - Publisher Copyright:
COPYRIGHT © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - We conducted a phase I dose-escalation study with 89Zr-desferrioxamine-IAB2M (89Zr-IAB2M), an anti-prostate-specific membrane antigen minibody, in patients with metastatic prostate cancer. Methods: Patients received 185 MBq (5 mCi) of 89Zr-IAB2M and Df-IAB2M at total mass doses of 10 (n = 6), 20 (n = 6), and 50 mg (n = 6). Wholebody and serum clearance, normal-organ and lesion uptake, and radiation absorbed dose were estimated, and the effect of mass escalation was analyzed. Results: Eighteen patients were injected and scanned without side effects. Whole-body clearance was monoexponential, with a median biologic half-life of 215 h, whereas serum clearance showed biexponential kinetics, with a median biologic half-life of 3.7 (12.3%/L) and 33.8 h (17.9%/L). The radiation absorbed dose estimates were 1.67, 1.36, and 0.32 mGy/MBq to liver, kidney, and marrow, respectively, with an effective dose of 0.41mSv/MBq (1.5 rem/mCi). Both skeletal and nodal lesions were detected with 89Zr-IAB2M, most visualized by 48-h imaging. Conclusion: 89Zr-IAB2M is safe and demonstrates favorable biodistribution and kinetics for targeting metastatic prostate cancer. Imaging with 10 mg of minibody mass provides optimal biodistribution, and imaging at 48 h after injection provides good lesion visualization. Assessment of lesion targeting is being studied in detail in an expansion cohort.
AB - We conducted a phase I dose-escalation study with 89Zr-desferrioxamine-IAB2M (89Zr-IAB2M), an anti-prostate-specific membrane antigen minibody, in patients with metastatic prostate cancer. Methods: Patients received 185 MBq (5 mCi) of 89Zr-IAB2M and Df-IAB2M at total mass doses of 10 (n = 6), 20 (n = 6), and 50 mg (n = 6). Wholebody and serum clearance, normal-organ and lesion uptake, and radiation absorbed dose were estimated, and the effect of mass escalation was analyzed. Results: Eighteen patients were injected and scanned without side effects. Whole-body clearance was monoexponential, with a median biologic half-life of 215 h, whereas serum clearance showed biexponential kinetics, with a median biologic half-life of 3.7 (12.3%/L) and 33.8 h (17.9%/L). The radiation absorbed dose estimates were 1.67, 1.36, and 0.32 mGy/MBq to liver, kidney, and marrow, respectively, with an effective dose of 0.41mSv/MBq (1.5 rem/mCi). Both skeletal and nodal lesions were detected with 89Zr-IAB2M, most visualized by 48-h imaging. Conclusion: 89Zr-IAB2M is safe and demonstrates favorable biodistribution and kinetics for targeting metastatic prostate cancer. Imaging with 10 mg of minibody mass provides optimal biodistribution, and imaging at 48 h after injection provides good lesion visualization. Assessment of lesion targeting is being studied in detail in an expansion cohort.
KW - 89Zr- IAB2M
KW - Dosimetry
KW - Minibody
KW - PSMA
KW - Prostate cancer imaging
UR - http://www.scopus.com/inward/record.url?scp=85001075179&partnerID=8YFLogxK
U2 - 10.2967/jnumed.116.176206
DO - 10.2967/jnumed.116.176206
M3 - Article
C2 - 27516450
AN - SCOPUS:85001075179
SN - 0161-5505
VL - 57
SP - 1858
EP - 1864
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 12
ER -