Dosimetric study of the ^99mTc-HYNIC-HDL nano system in a mouse model

High-density lipoproteins (HDL) are nano structures that specifically recognize the SR-B1 membrane receptor, which is over expressed in various types of cancer. Their structure favors the targeted transport of therapeutic and imaging agents, making them theranostic systems. HDL show long periods of circulation in the blood, which could limit their labeling with β-emitting radionuclides. One option to decrease this long blood circulation is to increase renal excretion. To do this, hydrophilic molecules are anchored to the surface of HDL. The HYNIC-HDL conjugated system may be an alternative to improve pharmacokinetic parameters, increasing renal excretion. The system, also radiolabeled with ^99mTc, becomes a theranostic nano system, since ^99mTc is anchored to the surface of HDL, indicating the site to which it is directed, while the nucleus will be available to carry a therapeutic agent. The objective of this work is to prepare and dosimetric ally evaluate the ^99mTc-HYNIC-HDL nano system in a murine model and compare its biodistribution and dosimetry with that reported for HDL individually. Cholesterol-HYNIC conjugate was prepared and HDL was added to the preparation. The nano structure was filtered with 0.22 µm filters to ensure a size smaller than 200 nm. The HYNIC-HDL were radiolabeled with ^99mTc. The ^99mTc-HYNIC-HDL system was purified by centrifugation with 30,000 Da MW CO membrane tubes. Healthy CD1 mice were injected with 100 µCi of the nano system and bio distributions were performed at times 0.5, 2, 4, and 24 h (3 mice per time). From the bio distributions, the radio pharmacokinetic model was determined and the absorbed dose per organ was calculated using the MIRD formalism and the OLINDA software. The obtained biodistribution was compared with that of the HDL/^99mTc-HYNIC-DA system in which ^99mTc-HYNIC-DA is internalized in the nucleus and the HDL surface is not modified. The bio distributions showed that the ^99mTc-HYNIC-HDL nano system has lower hepatobiliary excretion and higher renal excretion compared to HDL. This renal excretion was attributed to the presence of the hydrophilic sequence HYNIC. As a consequence of renal elimination, the absorbed dose in liver due to ^99mTc-HYNIC-HDL decreased compared to the absorbed dose produced by the HDL nano system/^99mTc-HYNIC-HDL decreased compared to the absorbed dose produced by the HDL nano system/^99mTc-HYNIC-DA, while renal increased, as expected. The ^99mTc-HYNIC-HDL conjugated nano system showed a lower absorbed dose to the liver and higher renal excretion compared to HDL/^99mTc-HYNIC-DA. Its dosimetric properties are suitable for use as a theranostic-specific recognition radiopharmaceutical in tumors that over express the SR-B1 receptor. (author)|