Radiolabeled porphyrin–antibody conjugates — A review of early work

Porphyrin–antibody conjugates have been examined for use in radiopharmaceuticals for both diagnostic and therapeutic applications. Here, all such conjugates wherein the porphyrin serves to chelate a radiometal are reviewed with emphasis on the molecular design, method of synthesis, and means of conjugation of the porphyrins. In each case, the porphyrins are equipped with four meso-aryl substituents (A 4 - or A 3 B-type) and no [Formula: see text]-pyrrole substituents. The number of porphyrins per antibody (i.e., conjugation ratio) is reported to range from 0.8 to 10. The radionuclides that have been chelated by the porphyrins include [Formula: see text]Cu(II), [Formula: see text]Cu(II), and [Formula: see text]In(III). While a handful of conjugation methods have been employed, most have relied on reaction between a porphyrin acyl motif and the [Formula: see text]-amino group of lysine. The respective binomial and Poissonian statistics of porphyrin formation and antibody derivatization are discussed. All reports concerning porphyrin–antibody conjugates wherein the porphyrin chelates a radiometal appeared in the period 1987–1997 from two research teams. The subsequent quiescence of this ostensibly promising research avenue is contrasted with the tremendous growth of other antibody-targeted therapies and the theranostic applications of radionuclides. Conjugates of radiolabeled porphyrins with antibodies were first prepared a generation ago for theranostics applications but have received little attention since. The present review focuses on molecular design and synthesis from that period.