Radiolytic decomposition of a radiopharmaceutical compositions containing radioactive iodine are stabilized by the incorporation therein of an effective amount of ascorbic acid, nicotinamide, nicotinic acid or combinations thereof.

The present invention provides a radiation-protecting agent which protects the active ingredient of radiopharmaceuticals against the radiolysis caused by a reaction of the active ingredient with water radicals formed by radiolysis of water, without decomposing the reactive active ingredient such as readily reducible active ingredient. The radiation-protecting agent of the present invention is characterized by comprising an organic compound usable in medical drugs and having high physiological acceptability and protecting the radiolabeled active ingredient of radiopharmaceuticals against the action of radiation. The reaction rate constant of said organic compound with OH radical, H radical or hydrated electron must be in the range of from 1.times.10.sup.8 to 5.times.10.sup.10 M.sup.-1 s.sup.-1, and when added to radiopharmaceuticals, molar concentration of the organic compound must be at least 50 times as high as molar concentration of the active ingredient.

N,N'-bis-(pyridoxal-5-phosphate)-alkylenediamine-N,N'-diacetic acids, N,N'-bis-(pyridoxal-5-phosphate)-1,2-cycloalkylenediamine-N,N'-diacetic acids, and N,N'-bis-(pyridoxal-5-phosphate)-1,2-arylenediamine-N,N'-diacetic acids, the corresponding monophosphate compounds and monoacetic acid compounds, and their salts and esters form stable, highly soluble chelates with paramagnetic metal ions, and are highly effective NMRI contrast agents. Preferred contrast agents are paramagnetic ion chelates of N,N'-bis-(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid, N,N'-bis-(pyridoxal-5-phosphate)trans-1,2-cyclohexylenediamine-N,N'diaceti c acid, N,N'-bis-(pyridoxal-5-phosphate)trans-1,2-arylenediamine-N,N'-diacetic acid, and the soluble calcium salts thereof. Novel intermediates for forming these compounds are N,N'-bis(pyridoxal-5-phosphate)alkylenediimines, N,N'-bis(pyridoxal-5-phosphate)alkylenediamines, N,N'-bis(pyridoxal-5-phosphate)-1,2-cycloalkylenediimines, N,N'-bis(pyridoxal-5-phosphate)-1,2-cycloalkylenediamines, N,N'-bis(pyridoxal-5-phosphate)-1,2-arylenediamines, and the corresponding monophosphate compounds.

A process for preparing a radiopharmaceutical composition comprising a technetium 99m chelate complex, comprises the steps of: (1) mixing (a) HSCH.sub.2 CO--NHCH.sub.2 CO--NHCH.sub.2 CO--NHCH.sub.2 COOH (mercaptoacetylglycylglycylglycine, MAG3), (b) a watersoluble reducing agent, (c) a water-soluble stabilizing agent in an amount of not less than 70 mol per 1 mol of the water-soluble reducing agent and (d) a pertechnetate at a pH of about 8 to 11; and (2) heating the resultant mixture at a temperature of about 90 to 140.degree. C. Said process removes any troublesome labeling operation at the diagnostic site and relieve the practitioners from the exposure to radiation during the labeling operation.

N,N'-bis-(pyridoxal-5-phosphate)-alkylenediamine-N,N'-diacetic acids, N,N'-bis-(pyridoxal-5-phosphate)-1,2-cycloalkylenediamine-N,N'-diacetic acids, and N,N'-bis-(pyridoxal-5-phosphate)-1,2-arylenediamine-N,N'-diacetic acids, the corresponding monophosphate compounds and monoacetic acid compounds, and their salts and esters form stable, highly soluble chelates with paramagnetic metal ions, and are highly effective NMRI contrast agents. Preferred contrast agents are paramagnetic ion chelates of N,N'-bis-(pyridoxal-5-phosphate)ethylene-diamine-N,N'-diacetic acid, N,N'-bis-(pyridoxal-5-phosphate)trans-1,2-cyclohexylenediamine-N,N'-diacet ic acid, N,N'-bis-(pyridoxal-5-phosphate)trans-1,2-arylenediamine-N,N'-diacetic acid, and the soluble calcium salts thereof. Novel intermediates for forming these compounds are N,N'-bis(pyridoxal-5-phosphate)alkylenediimines, N,N'-bis(pyridoxal-5-phosphate)alkylenediamines, N,N'-bis(pyridoxal-5-phosphate)-1,2-cycloalkylenediimines, N,N'-bis(pyridoxal-5-phosphate)-1,2-cycloalkylenediamines, N,N'-bis(pyridoxal-5-phosphate(-1,2-arylenediamines, and the corresponding monophosphate compounds.