Radiation Dosimetry, Pharmacokinetics, and Safety of Ultratrace™ Iobenguane I-131 in Patients with Malignant Pheochromocytoma/Paraganglioma or Metastatic Carcinoid

被引:44
作者
Coleman, R. Edward [1 ]
Stubbs, James B. [2 ]
Barrett, John A. [3 ]
de la Guardia, Miguel [3 ]
LaFrance, Norman [3 ]
Babich, John W. [3 ]
机构
[1] Duke Univ, Div Nucl Med, Med Ctr, Durham, NC 27710 USA
[2] Radiat Dosimetry Syst Inc, Palo Alto, CA USA
[3] Mol Insight Pharmaceut Inc, Cambridge, MA USA
关键词
pheochromocytoma; paraganglioma; carcinoid; neuroendocrine tumor; radiotherapy; MIBG; metaiodobenzylguanidine; Molecular Insight Pharmaceuticals; Ultratrace (131)I-MIBG; RADIONUCLIDE THERAPY; NUCLEAR-MEDICINE; METAIODOBENZYLGUANIDINE; PARAGANGLIOMA; MIBG;
D O I
10.1089/cbr.2008.0584
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
This is a first of many phase 1 study of Ultratrace (TM) Iobenguane I-131 (Ultratrace (131)I-MIBG; Molecular Insight Pharmaceuticals, Inc., Cambridge, MA). High-specific-activity Ultratrace (131)I-MIBG may provide improved efficacy and tolerability over carrier-added (131)I-MIBG. We investigated the pharmacokinetics (PK), radiation dosimetry, and clinical safety in 11 patients with confirmed pheochromocytoma/paraganglioma (Pheo) or carcinoid tumors. A single 5.0-mCi (185 MBq) injection of Ultratrace (131)I-MIBG, supplemented with 185 mu g of unlabeled MIBG to simulate the amount of MIBG anticipated in a therapeutic dose, was administered. Over 120 hours postdose, blood and urine were collected for PK, and sequential whole-body planar imaging was performed. Patients were followed for adverse events for 2 weeks. Ultratrace (131)I-MIBG is rapidly cleared from the blood and excreted in urine (80.3% +/- 2.8% of dose at 120 hours). For a therapeutic administration of 500 mCi (18.5 GBq), our estimate of the projected dose is 1.4 Gy for marrow and 10.4 Gy for kidneys. Safety results showed 12 mild adverse events, all considered unrelated to study drug, in 8 of 11 patients. These findings support the further development of Ultratrace (131)I-MIBG for the treatment of neuroendocrine tumors, such as metastatic Pheo and carcinoid.
引用
收藏
页码:469 / 475
页数:7
相关论文
共 20 条
  • [1] Boyd M, 2004, LETT DRUG DES DISCOV, V1, P50
  • [2] RADIONUCLIDE THERAPY OF PHEOCHROMOCYTOMAS AND NEUROBLASTOMAS USING I-131 METAIODOBENZYLGUANIDINE (MIBG)
    BRENDEL, AJ
    JEANDOT, R
    GUYOT, M
    LAMBERT, B
    DROUILLARD, J
    [J]. CLINICAL NUCLEAR MEDICINE, 1989, 14 (01) : 19 - 21
  • [3] Normal organ radiation dosimetry and associated uncertainties in nuclear medicine, with emphasis on iodine-131
    Brill, A. B.
    Stabin, M.
    Bouville, A.
    Ron, E.
    [J]. RADIATION RESEARCH, 2006, 166 (01) : 128 - 140
  • [4] *CIS US INC, 1999, IOB SULF 1 131 INJ D
  • [5] *DRAX INC, DRAX MIBG IOB 1 131
  • [6] TOLERANCE OF NORMAL TISSUE TO THERAPEUTIC IRRADIATION
    EMAMI, B
    LYMAN, J
    BROWN, A
    COIA, L
    GOITEIN, M
    MUNZENRIDER, JE
    SHANK, B
    SOLIN, LJ
    WESSON, M
    [J]. INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 1991, 21 (01): : 109 - 122
  • [7] Malignant pheochromocytomas and paragangliomas -: A phase II study of therapy with high-dose 131I-metaiodobenzylguanidine (131I-MIBG)
    Fitzgerald, Paul A.
    Goldsby, Robert E.
    Huberty, John P.
    Price, David C.
    Hawkins, Randall A.
    Veatch, Janet J.
    Dela Cruz, Filemon
    Jahan, Thierry M.
    Linker, Charles A.
    Damon, Lloyd
    Matthay, Katherine K.
    [J]. PHEOCHROMOCYTOMA, 2006, 1073 : 465 - 490
  • [8] Aspects on radionuclide therapy in malignant pheochromocytomas
    Forssell-Aronsson, Eva
    Bernhardt, Peter
    Kolby, Lars
    Nilsson, Ola
    Ahlman, Hakan
    [J]. PHEOCHROMOCYTOMA, 2006, 1073 : 498 - 504
  • [9] 131I-MIBG Therapy in metastatic phaeochromocytoma and paraganglioma
    Gedik, Gonca Kara
    Hoefnagel, Cornelis A.
    Bais, Evert
    Olmos, Renato A. Valdes
    [J]. EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 2008, 35 (04) : 725 - 733
  • [10] KVOLS LK, 2003, CANC MED