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

Abstract

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 mCi 111In 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Macromolecular Contrast Agents for Optical Imaging of Tumors: Comparison of Indotricarbocyanine-labeled Human Serum Albumin and Transferrin¶

“…The EPR effect is attributed to pathological alterations of tumor vasculature such as high density and increased permeability of the vessels and to an ineffective lymphatic drainage of tumor interstitium. Macromolecules could therefore be successfully used as carriers for the targeting of anticancer drugs to tumors (2,3). Moreover, the tumoritropic effect of macromolecules can be exploited for the delivery of covalently attached contrast agents to tumors for cancer diagnosis.…”

Pre-clinical evaluation of a methotrexate-albumin conjugate (MTX-HSA) in human tumor xenograftsin vivo

“…7,8 We have introduced a new albumin-MTX conjugate ( Fig. 14,15 Consequently, HSA was deemed feasible as a drug carrier and conjugates with MTX as chemotherapeutic agent were prepared. 9,10 The rationale for the design of this drug is based on the fact that plasma proteins constitute the major transportable nitrogen reserve in vertebrates.…”

“…13 Radiopharmacokinetic studies in laboratory animals and humans using radiolabeled HSA have revealed enhanced uptake and degradation of albumin by solid tumors. 14,15 Consequently, HSA was deemed feasible as a drug carrier and conjugates with MTX as chemotherapeutic agent were prepared. 16 -20 Interestingly, drug conjugates bearing multiple MTX molecules per albumin were rapidly cleared from circulation and predominately trapped by the monocyte-macrophage system of the liver.…”