Howard J. Glenn

Distribution and pharmacology of intravenous 99mTc-labeled multilamellar liposomes in rats and mice

Abstract The use of liposomes for the delivery of macrophage activators offers a new approach for the selective targeting of antitumor therapy. We have investigated the distribution, retention, and pharmacology of multilamellar liposomes (phosphatidylserine (PS): phosphatidylcholine (PC) 3:7) on i.v. injection in normal rats. Sprague-Dawley rats were injected with doses varying from 300 to 1000 mg/kg of 99m Tc-liposomes. The organ distribution of doses ranging from 300 to 500 mg/kg showed 45% mean uptake by liver, 25% by spleen, and 4% by lung. At higher doses of 800–1000 mg/kg, uptake in the lung increased significantly to 9 ± 3%. Whole body retention at 24 h after i.v. injection in Hale Stoner mice was 70%. The blood disappearance curve was biphasic and compared with the free isotope, a decrease was observed in the initial a phase t12 while the terminal phase t12 increased by 100%. These data suggest that encapsulation prolongs the initial distribution to the peripheral compartments and that higher doses may increase uptake by organs other than the liver.

Radiation dose and biological effects to mouse testis from sodium 32P-phosphate.

Radiation dose to mouse testis was estimated to be about 1.65 rad per microCi of intravenously injected 32P. This high dose to the organ was due to the incorporation of this isotope into the macromolecules of the testis. Up to 30% of the total testis activity was in DNA molecules. Biologic effects on mouse testis from 32P were determined by testis weight loss and the decrease in the number of sperm heads in the testis. Number of sperm heads reached a minimum of 1.3% of control 36 days after injection of 3.5 microCi/g body weight of 32P. Significant decreases in sperm head counts were observed after as little as 0.2 microCi/g body weight of 32P.

Iodohippurate Sodium 131I (OIH) Clearance in Mice Bioassay of Radiopharmaceuticals

Summary The renal plasma rates and modes of clearance of iodohippurate sodium 131I, 169Yb-DTPA, 113mIn-DTPA, and 99mTc-DTPA have been determined in mice and compared with those of inulin and OIH. The DTPA chelates or complexes of different radionuclides were found to be cleared by the mouse kidney by different pathways at surprisingly different rates. Clearance values were found to be closely reproducible, but should not be compared with values in man or other species. Iodohippurate sodium 131I can be used as a satisfactory clearance standard if it contains less than 1% free iodide in a formulation and concentration not toxic to renal function. The method reported has been shown to be a satisfactory bioassay for evaluating and comparing the clearance of radiopharmaceuticals of similar structure.

Radiation dose effects on mouse testis from sodium P-32 phosphate

Radiation dose and biological damage data to mouse testis from the internal administration of sodium P-32-phosphate are presented and the data compared with that from sodium Tc-99m-pertechnetate and external Cs-137 radiation. P-32 is shown to be more effective in damaging or killing differentiated spermatogonia, using the decrease in sperm head count technique. The radiation dose to mouse testis from one microcurie of P-32 phosphate was estimated to be 1.3 rads as compared with 4.9 rads from one millicurie of Tc-99m. For P-32, the LD/sub 50/ for survival of mouse spermatogonia was calculated to be about 36 rads as compared with 53 rads observed using external Cs-137 radiation. Part of the greater radiation dose to the testis can be attributed to the incorporation of P-32-phosphate into testicular macromolecules, primarily DNA, thus contributing to the prolonged residence time of the activity in the testis. From these limited comparisons, it appears that internally administered radiopharmaceuticals may cause relatively slightly more radiation damage to testis than external radiation.