Prodrugs in site-selective delivery of radiopharmaceuticals

Janina Baranowska-Kortylewicz, Z. P. Kortylewicz, D. Hoffman, G. V. Dalrymple

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

This paper review basic rules for the design of site-selective prodrugs and various modes of their activation with particular emphasis on the applications of prodrugs to targeted delivery of radiopharmaceutical. Although many radiopharmaceuticals are 'targeted' to specific tissues or organs, we will discuss only agents that are either chemically or metabolically transformed producing an active form that is retained by its target. Site-specific prodrugs of diagnostic radiopharmaceuticals are routine in the nuclear medicine applications, but the instances of targeting the radiotherapeutic prodrugs are surprisingly rare. We have concentrated on our own efforts to design and synthesize site-selective prodrugs of 5- [125I]iodo-2'deoxyuridine (125IUdR) for cancer radiotherapy. The prodrugs of 125IUdR for targeted delivery include several derivatives with altered permeability, 3',5'-dioctanoyl, 3',5'-dioleoyl, 3'- and 5'-N-alkyl- dihydropyridyl, 3'- and 5'-N-alkyl-dihydroisoquionolyl, and 3'- and 5'- N- alkyl-dihydroacridinyl esters of 125IUdR; polymeric and macromolecular prodrugs of 125IUdR for a carrier-mediated or local delivery; metabolically trapped 125-IUdR prodrugs; and glycoconjugate prodrugs for oral colon-specific delivery of 125IU(D)R. 125IU(D)R-5'-β-d- cellobioside, 125IU(D)R-5'β-(D)-glucopyranoside, 125IU(D)R-5'β-(D)- galactopyranoside and 125IU(D)R-5'-β-(D)-glucuronide. We also describe prodrugs of several diagnostic agents in the context of the metabolic trapping as the primary targeting modality. For various diagnostic agents the prodrug target-associated enzymes are discussed and examples of the site- specific release of active agent are given. A brief overview of an emerging role of residualizing labels in radioimmunotherapy is included.

Original languageEnglish (US)
Pages (from-to)127-139
Number of pages13
JournalQuarterly Journal of Nuclear Medicine
Volume41
Issue number2
StatePublished - Jul 3 1997

Fingerprint

Radiopharmaceuticals
Prodrugs
Idoxuridine
Radioimmunotherapy
Deoxyuridine
Glycoconjugates
Nuclear Medicine
Glucuronides
Galactose
Permeability
Colon
Esters
Radiotherapy

Keywords

  • Prodrugs
  • Radiopharmaceuticals
  • Site-specific delivery
  • Tumor targeting

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Baranowska-Kortylewicz, J., Kortylewicz, Z. P., Hoffman, D., & Dalrymple, G. V. (1997). Prodrugs in site-selective delivery of radiopharmaceuticals. Quarterly Journal of Nuclear Medicine, 41(2), 127-139.

Prodrugs in site-selective delivery of radiopharmaceuticals. / Baranowska-Kortylewicz, Janina; Kortylewicz, Z. P.; Hoffman, D.; Dalrymple, G. V.

In: Quarterly Journal of Nuclear Medicine, Vol. 41, No. 2, 03.07.1997, p. 127-139.

Research output: Contribution to journalArticle

Baranowska-Kortylewicz, J, Kortylewicz, ZP, Hoffman, D & Dalrymple, GV 1997, 'Prodrugs in site-selective delivery of radiopharmaceuticals', Quarterly Journal of Nuclear Medicine, vol. 41, no. 2, pp. 127-139.
Baranowska-Kortylewicz, Janina ; Kortylewicz, Z. P. ; Hoffman, D. ; Dalrymple, G. V. / Prodrugs in site-selective delivery of radiopharmaceuticals. In: Quarterly Journal of Nuclear Medicine. 1997 ; Vol. 41, No. 2. pp. 127-139.
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