Optimal radiolabeled liposomes for tumor imaging

We conducted a systematic study of the effects of liposome formulation and encapsulated radionuclides on imaging ability.

Various types of liposomes were prepared and labeled with 67Ga, 111In or 99mTc. Their tumor-imaging potential was evaluated in terms of tumor accumulation and tumor-to-blood ratios of radioactivity delivered by the liposomes. Mouse sarcoma 180 and Ehrlich solid tumor were the tumor models.

Liposomes could be labeled rapidly and with high efficiency, which was sufficient for clinical application. Tumor accumulation of liposome-encapsulated radionuclides that have intrinsic tumor affinity, such as 67Ga-NTA or 111In-NTA, was larger than that of the other nuclides. Liposomes that were fairly small, cholesterol-rich and composed of so-called rigid phospholipids, could deliver large amounts of encapsulated radionuclides to the tumor. We also found that tumor uptake of such liposomes was large and their blood retention was prolonged. Liposomal lipid dose also influenced tumor delivery and blood retention. The results suggest that these factors extended liposomal blood retention and, consequently, increased tumor uptake of the liposomes and tumor delivery of encapsulated radionuclides. Not all liposomes with long blood retention, however, are suitable for tumor imaging. Incorporation of monosialo-ganglioside in the liposomal membrane greatly extended blood retention but increased tumor uptake only slightly and, consequently, made the tumor-to-blood value worse. One of the 67Ga-labeled liposome formulations resulted in high tumor uptake and tumor-to-blood ratios in various tumor models as well as clearly visualized tumors clearly in sarcoma 180-bearing mice.

For tumor imaging with radiolabeled liposomes, we should choose liposomal formulations and dose to give prolonged blood retention for large tumor delivery. We must then select liposomes that give good tumor-to-blood values. For the best results, the radionuclide should have intrinsic tumor affinity. Labeled liposomes that meet these criteria result in excellent tumor images.