In a new therapy that aims to concentrate and immobilize therapeutic radionuclides in nanoscale assemblies within solid tumors, a soluble precipitable reagent (SPR) is administered as the radionuclide carrier and is converted to non-diffusible precipitate by an enzyme located in tumor tissues. To meet the objective of such an SPR, we have prepared and examined a class of porphyrin–alkyldiphosphates that are soluble in aqueous solution and that are rendered insoluble upon removal of the two phosphate groups. The porphyrins examined herein are of the trans-AB architecture wherein the substituents are a bis(dihydroxyphosphoryloxy)alkyl group and a phenyl (or p-bromophenyl) group. Provisions for later incorporation of radionuclides have been established by preparation of the analogous copper chelate or the meso-iodo free-base porphyrin. Altogether, four porphyrins bearing a bis(dihydroxyphosphoryloxy)alkyl group were examined and found to exhibit satisfactory solubility in water (>1 mM). Dephosphorylation reactions have been carried out in vitro using the enzyme shrimp alkaline phosphatase. In each case, enzyme-induced precipitation was observed. The soluble-to-insoluble conversion has been examined by visual inspection, absorption spectroscopy, electrospray ionization mass spectrometry, and nephelometry using non-radiolabeled porphyrins.