SERUM-ALBUMIN (SA) ACCUMULATION BY BRONCHOGENIC TUMORS - A TRACER TECHNIQUE MAY HELP WITH PATIENT SELECTION FOR SA-DELIVERED CHEMOTHERAPY

Systemic toxicity and inadequate tumour uptake of chemotherapeutic age nts limit effective therapy of disseminated malignant disease. We seek to use macromolecules for improved delivery of therapeutic agents to tumours, and hope to use radiotracer procedures to identify those mali gnancies able to accumulate the transport molecule. A literature searc h identified in vitro and animal experimental data which indicated tha t serum albumin is taken up in malignancies. Selected cytostatic drugs can be bound to albumin, which suggests the suitability of the molecu le as a potential transport vehicle. We therefore evaluated indium-111 labelled human serum albumin (HSA) to determine the frequency of its accumulation in bronchogenic tumours. Single-photon emission tomograph ic (SPET) images were obtained in 23 patients 48 h after intravenous i njection of 1.5 mCi In-111 diethylenetriamine penta-acetic acid (DTPA) -HSA. SPET imaging with technetium-99m labelled erythrocytes was inclu ded in the protocol to assess the influence which vascularity has on t he HSA-based images. All patients went on to surgery. We documented th e histological diagnosis, T-stage and differentiation grade. The scint igraphic examination demonstrated HSA uptake in three squamous cell ca rcinomas and four adenocarcinomas. Of these, six malignancies accumula ting HSA had 2.2-5.4 times the tracer concentrations observed in compa rable background regions. Small cell carcinoma failed to accumulate th e labelled HSA during the 2-day scintigraphic evaluation. The PISA ima ges did not appear to represent tumour vascularity. T-stage and differ entiation grade failed to predict which tumours would demonstrate HSA uptake. Initial results suggest that HSA merits evaluation as a potent ial transport molecule for tumour-directed therapeutic agents, since a pproximately 35% of the examined malignancies showed HSA uptake. At th e same time the relatively infrequent tumour HSA incorporation may man date using scintigraphy and labelled HSA for selecting those individua ls who may profit from HSA-delivered drug therapy. The described selec tion and therapy approach was tried in two patients who had an In-111- DTPA-HSA tumour to background ratio of 1.45:1 and 5.3:1 respectively. Both received experimental chemotherapy with methotrexate (MTX)-HSA.