Enhanced Albumin Uptake by Rat Tumors

Albumin dominates the nitrogen and energy resources in blood. However, only limited data is available on its accumulation and catabolism by tumors. This was caused by the lack of suitable radiolabels for long-term follow-up of protein catabolism in vivo. Conventional radiolabels like radioiodine are metabolically unstable. After lysosomal degradation diffusible tracer residues are rapidly released from catabolic sites, Tumors with high metabolic activity evade detection. To study the uptake of rat serum albumin (RSA) by tumors a conventional radioiodine label and two residualizing radiolabels were chosen. It is known that residualizing I-131-tyramine-deoxisorbitol and In-111-DTPA protein labels remain trapped at catabolic sites after lysosomal degradation of their carrier proteins. We were able to show by scintigraphy and after organ removal that a Walker-256 carcinosarcoma with a turner size of about 5% of the body weight accumulated more than 20% of the initially injected dose of a In-111-DTPA-RSA within 24 h. Tumor uptake rates for albumin exceeded those of the kidneys by about 4 times, and those of the liver by about 3 times. It was estimated that about one out of two albumin molecules trapped by an ovarian-342 tumor must have been degraded during 72 h. High uptake and degradation rates would make albumin an alternative nitrogen and energy source for these tumors. Although an unfavorable time-frame limits the use of residualizingly labeled albumin for scintigraphic tumor diagnosis in man, albumin might be an interesting carrier for delivering covalently attached chemotherapeutic agents into tumors by an alternative lysosomal route.