Abstract
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-965. 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-965 infusion demonstrated a significant drop [P < 0.001] in the liver/heart ratio of radioactivity [251 ± 035 (SEM)] compared to patients receiving the identical dose of NIR-MoAb [1035 ± 133]. Significant decreases in spleen/heart and bone/heart ratios were also observed. Pharmacokinetic studies showed that the volume of distribution (Vd) and the plasma t2 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 < 0.05). Although tissue distribution of 111In-labeled antibody can be ascribed to nonspecific organ clearance of murine antibodies, a substantial component of tissue disposition of antibody 96.5 was shown to be a consequence of specific clearance of immunoreactive antibody which may cross-react with tissue antigens.
| Original language | English |
|---|---|
| Pages (from-to) | 4417-4422 |
| Number of pages | 6 |
| Journal | Cancer Research |
| Volume | 48 |
| Issue number | 15 |
| Publication status | Published - 1988 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Immunospecific Saturable Clearance Mechanisms for Indium-111-labeled Anti-Melanoma Monoclonal Antibody 96.5 in Humans. / Murray, James L.; Lamki, Lamk M.; Shanken, Linda J.; Blake, Mary E.; Plager, Carl E.; Benjamin, Robert S.; Schweighardt, Sally; Unger, Michael W.; Rosenblum, Michael G.
In: Cancer Research, Vol. 48, No. 15, 1988, p. 4417-4422.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Immunospecific Saturable Clearance Mechanisms for Indium-111-labeled Anti-Melanoma Monoclonal Antibody 96.5 in Humans
AU - Murray, James L.
AU - Lamki, Lamk M.
AU - Shanken, Linda J.
AU - Blake, Mary E.
AU - Plager, Carl E.
AU - Benjamin, Robert S.
AU - Schweighardt, Sally
AU - Unger, Michael W.
AU - Rosenblum, Michael G.
PY - 1988
Y1 - 1988
N2 - 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-965. 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-965 infusion demonstrated a significant drop [P < 0.001] in the liver/heart ratio of radioactivity [251 ± 035 (SEM)] compared to patients receiving the identical dose of NIR-MoAb [1035 ± 133]. Significant decreases in spleen/heart and bone/heart ratios were also observed. Pharmacokinetic studies showed that the volume of distribution (Vd) and the plasma t2 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 < 0.05). Although tissue distribution of 111In-labeled antibody can be ascribed to nonspecific organ clearance of murine antibodies, a substantial component of tissue disposition of antibody 96.5 was shown to be a consequence of specific clearance of immunoreactive antibody which may cross-react with tissue antigens.
AB - 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-965. 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-965 infusion demonstrated a significant drop [P < 0.001] in the liver/heart ratio of radioactivity [251 ± 035 (SEM)] compared to patients receiving the identical dose of NIR-MoAb [1035 ± 133]. Significant decreases in spleen/heart and bone/heart ratios were also observed. Pharmacokinetic studies showed that the volume of distribution (Vd) and the plasma t2 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 < 0.05). Although tissue distribution of 111In-labeled antibody can be ascribed to nonspecific organ clearance of murine antibodies, a substantial component of tissue disposition of antibody 96.5 was shown to be a consequence of specific clearance of immunoreactive antibody which may cross-react with tissue antigens.
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UR - http://www.scopus.com/inward/citedby.url?scp=0023696139&partnerID=8YFLogxK
M3 - Article
C2 - 3390837
AN - SCOPUS:0023696139
VL - 48
SP - 4417
EP - 4422
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 15
ER -