Serum albumin (SA) accumulation by bronchogenic tumours: a tracer technique may help with patient selection for SA-delivered chemotherapy

Systemic toxicity and inadequate tumour uptake of chemotherapeutic agents 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 malignancies able to accumulate the transport molecule. A literature search identified in vitro and animal experimental data which indicated that serum albumin is taken up in malignancies. Selected cytostatic drugs can be bound to albumin, which suggests the suitability of the molecule 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 tomographic (SPET) images were obtained in 23 patients 48 h after intravenous injection of 1.5 mCi¹¹¹In diethylenetriamine penta-acetic acid (DTPA)-HSA. SPET imaging with technetium-99m labelled erythrocytes was included in the protocol to assess the influence which vascularity has on the HSA-based images. All patients went on to surgery. We documented the histological diagnosis, T-stage and differentiation grade. The scintigraphic examination demonstrated HSA uptake in three squamous cell carcinomas and four adenocarcinomas. Of these, six malignancies accumulating HSA had 2.2–5.4 times the tracer concentrations observed in comparable background regions. Small cell carcinoma failed to accumulate the labelled HSA during the 2-day scintigraphic evaluation. The HSA images did not appear to represent tumour vascularity. T-stage and differentiation grade failed to predict which tumours would demonstrate HSA uptake. Initial results suggest that HSA merits evaluation as a potential transport molecule for inmour-directed therapeutic agents, since approximately 35% of the examined malignancies showed HSA uptake. At the same time the relatively infrequent tumour HSA incorporation may mandate using scintigraphy and labelled HSA for selecting those individuals who may profit from HSA-delivered drug therapy. The described selection and therapy approach was tried in two patients who had an¹¹¹In-DTPA-HSA tumour to background ratio of 1.45:1 and 5.3:1 respectively. Both received experimental chemotherapy with methotrexate (MTX)-HSA.