Immunospecific saturable clearance mechanisms for indium-111-labeled anti-melanoma monoclonal antibody 96. 5 in humans
Liver uptake of 111In-labeled monoclonal antibodies (MoAb) remains a significant problem in radioimaging studies to date. To determine if the observed liver uptake of an 111In-labeled anti-melanoma antibody 96.5 (111In-96.5) was dependent on the presence of hepatic antigen or on recognition of circulating murine antibody, escalating doses of an unlabeled nonimmunoreactive MoAb (NIR-MoAb) were administered to 18 patients with metastatic malignant melanoma either 1 or 24 h prior to an infusion of 1 mg of 111In-96.5. The number of metastases imaged, pharmacokinetics, and the ratio of radioactivity (expressed as average counts/pixel) in liver (L), spleen (S), bone (B), and kidney (K) compared to blood pool (heart = H) were examined. Results were prospectively compared with data from six patients who received immunoreactive unlabeled 96.5 prior to 111In-96.5. Increasing dose or changes in the preinfusion time of NIR-MoAb had no significant effect on the biodistribution of 111In-96.5. In contrast, patients who received unlabeled, immunoreactive 96.5 prior to 111In-96.5 infusion demonstrated a significant drop (P less than 0.001) in the liver/heart ratio of radioactivity (2.81 +/- 0.35 (SEM)) compared to patients receiving the identical dose of NIR-MoAb (10.35 +/- 1.33). Significant decreases in spleen/heart and bone/heart ratios were also observed. Pharmacokinetic studies showed that the volume of distribution (Vd) and the plasma t1/2 both decreased when 96.5 was administered compared to NIR-MoAb. In addition, a 4-fold increase in concentration X time was obtained after 96.5 antibody was administered compared to NIR-MoAb. More metastases were imaged in patients receiving preinfusions of 96.5 (23 of 28) than in patients receiving NIR-MoAb (10 of 18; P less than 0.05).
- Research Organization:
- Univ. of Texas M. D. Anderson Cancer Center, Houston (USA)
- OSTI ID:
- 7001611
- Journal Information:
- Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 48:15; ISSN CNREA
- Country of Publication:
- United States
- Language:
- English
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62 RADIOLOGY AND NUCLEAR MEDICINE
ANTIBODIES
BETA DECAY RADIOISOTOPES
BIOLOGICAL HALF-LIFE
BODY
CARDIOVASCULAR SYSTEM
CLEARANCE
DAYS LIVING RADIOISOTOPES
DIAGNOSIS
DIAGNOSTIC USES
DIGESTIVE SYSTEM
DISEASES
DISTRIBUTION
ELECTRON CAPTURE RADIOISOTOPES
GLANDS
HEART
IMMUNE REACTIONS
INDIUM 111
INDIUM ISOTOPES
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
KIDNEYS
LIVER
MELANOMAS
MINUTES LIVING RADIOISOTOPES
MONOCLONAL ANTIBODIES
MUSCLES
MYOCARDIUM
NEOPLASMS
NUCLEI
ODD-EVEN NUCLEI
ORGANS
PATIENTS
RADIOISOTOPES
SKELETON
SPLEEN
TISSUE DISTRIBUTION
UPTAKE
USES