A new method for delivering radioactive cytotoxic agents in solid cancers.
OBJECTIVE
Therapeutic agents such as monoclonal antibodies, radiopharmaceuticals, and radioactive growth factors are limited in effectiveness due to the inability to deposit significant quantities of the agents and for limited periods of time in solid cancer. A new technique based on knowledge of the pathophysiology of solid tumors allows for significant concentration of these agents to accumulate and for a prolonged period of time, thus allowing interaction with the tumor for potentially increased effectiveness.


METHODS
Three agents have been studied: 131I antiferritin monoclonal antibody, colloidal 32P chromic phosphate, and 131I transferrin. The time required for maximal tumor uptake was determined in vitro in tissue culture and was 10 min, 25 min, and 40 min, respectively. The new method of in vivo tumor infusion consisted of a direct intratumoral injection of macroaggregated albumin (MAA) 10,000 particles, followed by the radioactive agents under study. Tumors were infused in vivo using the new technique and compared to intratumoral infused controls. In the instance of radiolabeled antiferritin antibody, intraperitoneal administration and intratumoral infusion were compared to the new technique. In the other two instances, intratumoral infusion was compared to the new method.


RESULTS
In all instances the direct vascular blockade caused by MAA led to greater deposition of the agent under study for at least 24 h. These results were clinically applied with MAA followed by 32P colloidal chromic phosphate and were consistent with the experimental findings.


CONCLUSIONS
A new technique is described that may be carried out in the experimental laboratory and clinic by direct tumor infusion of macroaggregated albumin (MAA), followed by other radioactive agents that will remain localized in solid cancers and will allow for high tumor dose deposition for potentially increased therapeutic efficacy.
Order
S E
SE
Department of Radiation Oncology, Cooper Hospital/University Medical Center, Camden, NJ 08103.
Siegel
J A
JA
Lustig
R A
RA
Principato
R
R
Zeiger
L S
LS
Johnson
E
E
Zhang
H
H
Lang
P
P
Pilchik
N B
NB
Metz
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage; D003102:Colloids; D003603:Cytotoxins / Q000008:administration & dosage; D005293:Ferritins / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes / Q000008:administration & dosage*; D008113:Liver Neoplasms / Q000532:radiotherapy; D051379:Mice; D008819:Mice, Nude; D010761:Phosphorus Radioisotopes / Q000008:administration & dosage*; D051381:Rats; D014168:Transferrin / Q000737:chemistry*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D003102:Colloids; D003603:Cytotoxins; D007457:Iodine Radioisotopes; D010761:Phosphorus Radioisotopes; D014168:Transferrin; D005293:Ferritins