Targeted systemic
radiotherapy constitutes the systemic administration of a radioactive agent that targets a molecule expressed preferentially on
cancer cells. The archetypal such
therapy is 131-iodine ((131)I)
therapy for differentiated
thyroid cancers.
Radiotherapy typically delivers a calculated radiation-absorbed dose to
tumor that takes into account (contiguous) normal tissue. Systemic
radiotherapy development currently uses schema more analogous to
chemotherapy--a radioactivity estimate that does not cause any irreversible toxicity. Historically, arbitrary amounts of radioactivity shown to be effective, on the basis of retrospective review, were used for
thyroid cancer therapy with (131)I as well as for
neuroendocrine tumor therapy with (131)I-labeled meta-iodo-
benzylguanidine (
MIBG). Their established safety record has led to adaptations that include repeat
therapies with nontoxic amounts of radioactivity. There remains, however, a lack of clear understanding of the safety limits of systemic
targeted radiotherapy. This is probably most true in systemic
therapy with
MIBG in adult
neuroendocrine tumors. Bone marrow is the primary critical organ for most targeted systemic
radiotherapy; second organ involvement may be renal, as with
MIBG and targeted radiopeptide
therapy, or pulmonary, as with
radioimmunotherapy. Most
therapies have tended toward multiple administrations of subtoxic amounts of radioactivity.
Therapy with
MIBG in pheochromococytoma as well as targeted radiopeptide
therapy in
medullary thyroid cancer has followed this model.
Radioimmunotherapy appears very promising; a definitive Phase 2 study needs completion. All
therapy has shown promise in extending disease survival (as compared with historical controls), with few major structural (or biochemical) responses. This review will attempt to compliment the excellent existing literature by providing an overall systemic therapeutic approach to this promising endeavor.