Biodistribution and pharmacokinetic screening in humans of monoclonal antibody AR-3 as a possible immunoscintigraphy agent in patients with pancreatic cancer

G. Mariani, N. Molea, D. Bacciardi, U. Boggi, C. Bonino, A. Costa, P. Viacava, M. Castagna, L. Bodei, L. Tarditi, P. C. Giulianotti, F. Vitek

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Abstract

This pharmacokinetic study was performed in order to assess the potential usefulness of the murine monoclonal antibody (MoAb) AR-3-IgG1 as an immunoscintigraphy agent for pancreatic cancer. This MoAb, which defines a mucin-like antigen (CAR-3) expressed by a large fraction of pancreatic cancers, shows in fact favourable in vivo localizing properties in the experimental animal model of human tumor xenograft. 131I-AR-3-IgG1 was injected i.v. into 5 patients with suspected pancreatic cancer. Whole-body maps and spot views of the abdominal area were recorded with a computerized gamma-camera, and specific regions of interest drawn over the liver and spleen helped to define the kinetics of activity in these organs. Blood samples taken from 0.1-144 hours post-injection and daily urine collections over the same interval served to define the kinetics of plama distribution and removal of activity from the body. Different multicompartmental models were tested to fit the experimental data, assuming as the starting hypothesis that there was to be significant nonspecific tracer accumulation in the liver, spleen and bone marrow, as already observed for the majority of radioiodinated murine MoAbs injected into humans. Surgery confirmed pancreatic cancer in 3 out of the 5 patients (chronic pancreatitis and periampullary cancer in one each); in all these 3 patients immunostaining with the MoAb AR-3 demonstrated the presence of the CAR-3 antigen (with a cytoplasmic and endoluminal/secretory pattern of distribution). Nonspecific radioactivity accumulation in the liver, spleen and bone marrow was extremely low, linked essentially to the blood pool effect of circulating activity in these organs. Although the overall quality of scintigraphic maps recorded over the abdomen was quite satisfactory (due to the low liver and spleen activity), scintigraphic demonstration of the pancreatic cancers was rather weak in 2 of the 3 cancer patients, and negative in the third patient (in whom the tumor was smaller than 2 cm in size). The overall pharmacokinetic pattern of distribution of MoAb 131I-AR-3 IgG1 was found to be best described by a reduced multicompartmental model in which the occurrence of nonspecific tracer uptake in the liver, spleen and bone marrow could be excluded, with the tracer simply exchanging between plasma and an extravascular space in which a certain fraction of catabolism also took place. The results obtained in this study confirm that the preliminary biodistribution screening in humans of potential MoAb immunoscintigraphy agents is an essential requirement even for MoAbs showing favourable tumor targeting properties in the experimental animal model.

Original languageEnglish
Pages (from-to)145-150
Number of pages6
JournalJournal of nuclear biology and medicine (Turin, Italy : 1991)
Volume38
Issue number4 SUPPL. 1
Publication statusPublished - 1994

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Proxy
Pancreatic Neoplasms
Spleen
Pharmacokinetics
Monoclonal Antibodies
Liver
Immunoglobulin G
Bone Marrow
Neoplasms
Animal Models
Urine Specimen Collection
Gamma Cameras
Chronic Pancreatitis
Mucins
Heterografts
Abdomen
Radioactivity
Injections
CAR-3 antigen

Keywords

  • biodistribution pharmacokinetics
  • monoclonal antibody
  • multicompartmental modeling
  • pancreatic cancer
  • tumor immunoscintigraphy

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Biodistribution and pharmacokinetic screening in humans of monoclonal antibody AR-3 as a possible immunoscintigraphy agent in patients with pancreatic cancer. / Mariani, G.; Molea, N.; Bacciardi, D.; Boggi, U.; Bonino, C.; Costa, A.; Viacava, P.; Castagna, M.; Bodei, L.; Tarditi, L.; Giulianotti, P. C.; Vitek, F.

In: Journal of nuclear biology and medicine (Turin, Italy : 1991), Vol. 38, No. 4 SUPPL. 1, 1994, p. 145-150.

Research output: Contribution to journalArticle

Mariani, G, Molea, N, Bacciardi, D, Boggi, U, Bonino, C, Costa, A, Viacava, P, Castagna, M, Bodei, L, Tarditi, L, Giulianotti, PC & Vitek, F 1994, 'Biodistribution and pharmacokinetic screening in humans of monoclonal antibody AR-3 as a possible immunoscintigraphy agent in patients with pancreatic cancer', Journal of nuclear biology and medicine (Turin, Italy : 1991), vol. 38, no. 4 SUPPL. 1, pp. 145-150.
Mariani, G. ; Molea, N. ; Bacciardi, D. ; Boggi, U. ; Bonino, C. ; Costa, A. ; Viacava, P. ; Castagna, M. ; Bodei, L. ; Tarditi, L. ; Giulianotti, P. C. ; Vitek, F. / Biodistribution and pharmacokinetic screening in humans of monoclonal antibody AR-3 as a possible immunoscintigraphy agent in patients with pancreatic cancer. In: Journal of nuclear biology and medicine (Turin, Italy : 1991). 1994 ; Vol. 38, No. 4 SUPPL. 1. pp. 145-150.
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AU - Boggi, U.

AU - Bonino, C.

AU - Costa, A.

AU - Viacava, P.

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N2 - This pharmacokinetic study was performed in order to assess the potential usefulness of the murine monoclonal antibody (MoAb) AR-3-IgG1 as an immunoscintigraphy agent for pancreatic cancer. This MoAb, which defines a mucin-like antigen (CAR-3) expressed by a large fraction of pancreatic cancers, shows in fact favourable in vivo localizing properties in the experimental animal model of human tumor xenograft. 131I-AR-3-IgG1 was injected i.v. into 5 patients with suspected pancreatic cancer. Whole-body maps and spot views of the abdominal area were recorded with a computerized gamma-camera, and specific regions of interest drawn over the liver and spleen helped to define the kinetics of activity in these organs. Blood samples taken from 0.1-144 hours post-injection and daily urine collections over the same interval served to define the kinetics of plama distribution and removal of activity from the body. Different multicompartmental models were tested to fit the experimental data, assuming as the starting hypothesis that there was to be significant nonspecific tracer accumulation in the liver, spleen and bone marrow, as already observed for the majority of radioiodinated murine MoAbs injected into humans. Surgery confirmed pancreatic cancer in 3 out of the 5 patients (chronic pancreatitis and periampullary cancer in one each); in all these 3 patients immunostaining with the MoAb AR-3 demonstrated the presence of the CAR-3 antigen (with a cytoplasmic and endoluminal/secretory pattern of distribution). Nonspecific radioactivity accumulation in the liver, spleen and bone marrow was extremely low, linked essentially to the blood pool effect of circulating activity in these organs. Although the overall quality of scintigraphic maps recorded over the abdomen was quite satisfactory (due to the low liver and spleen activity), scintigraphic demonstration of the pancreatic cancers was rather weak in 2 of the 3 cancer patients, and negative in the third patient (in whom the tumor was smaller than 2 cm in size). The overall pharmacokinetic pattern of distribution of MoAb 131I-AR-3 IgG1 was found to be best described by a reduced multicompartmental model in which the occurrence of nonspecific tracer uptake in the liver, spleen and bone marrow could be excluded, with the tracer simply exchanging between plasma and an extravascular space in which a certain fraction of catabolism also took place. The results obtained in this study confirm that the preliminary biodistribution screening in humans of potential MoAb immunoscintigraphy agents is an essential requirement even for MoAbs showing favourable tumor targeting properties in the experimental animal model.

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