HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Potential increased tumor-dose delivery with combined 131I-MIBG and 90Y-DOTATOC treatment in neuroendocrine tumors: a theoretic model.

AbstractUNLABELLED:
(131)I-Metaiodobenzylguanidine (MIBG) and (90)Y-DOTA-D-Phe1-Tyr3-octreotide (DOTATOC) have been used as radiotherapeutic agents for treating neuroendocrine tumors. The tumor dose delivered by these agents is often insufficient to control or cure the disease. However, these 2 agents used together could potentially increase tumor dose without exceeding the critical organ dose because the dose-limiting tissues are different. In this paper, we investigate the conditions in which combined-agent therapy is advantageous and we quantify the expected tumor-dose gain.
METHODS:
A series of equations was derived that predicted the optimal combination of agents and the fractional increase in tumor dose available from combined-agent therapy with respect to either (131)I-MIBG or (90)Y-DOTATOC. The results obtained from these derivations were compared with direct dose calculations using published dosimetric organ values for (131)I-MIBG and (90)Y-DOTATOC along with critical organ-dose limits. Tumor dose was calculated as a function of the tumor-dose ratio, defined as the (90)Y-DOTATOC tumor dose per megabecquerel divided by the (131)I-MIBG tumor dose per megabecquerel. Comparisons were made between the dose delivered to tumor with single-agent therapy and the dose delivered to tumor with combined-agent therapy as a function of the tumor-dose ratio and the fraction of activity contributed by each agent.
RESULTS:
The dose model accurately predicted the optimal combination of agents, the range at which combined-agent therapy was advantageous, and the magnitude of the increase. For the published organ dosimetry and critical organ-dose limits, combined-agent therapy increased tumor dose when the tumor-dose ratio was greater than 0.67 and less than 5.93. The maximum combined-agent tumor-dose increase of 68% occurred for a tumor-dose ratio of 2.57, using 92% of the maximum tolerated (90)Y-DOTATOC activity supplemented with 76% of the maximum tolerated activity of (131)I-MIBG. Variations in organ dose per megabecquerel and dose-limiting values altered both the magnitude of the increase and the range at which combined-agent therapy was advantageous.
CONCLUSION:
Combining (131)I-MIBG and (90)Y-DOTATOC for radiotherapy of neuroendocrine tumors can significantly increase the delivered tumor dose over the dose obtained from using either agent alone. Prior knowledge of the normal-organ and tumor dosimetry of both agents is required to determine the magnitude of the increase.
AuthorsMark T Madsen, David L Bushnell, Malik E Juweid, Yusuf Menda, M Sue O'Dorisio, Thomas O'Dorisio, Ian M Besse
JournalJournal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 47 Issue 4 Pg. 660-7 (Apr 2006) ISSN: 0161-5505 [Print] United States
PMID16595501 (Publication Type: Journal Article)
Chemical References
  • Iodine Radioisotopes
  • Radiopharmaceuticals
  • Yttrium Radioisotopes
  • 3-Iodobenzylguanidine
  • Octreotide
  • Edotreotide
Topics
  • 3-Iodobenzylguanidine (pharmacokinetics, therapeutic use)
  • Drug Therapy, Combination
  • Humans
  • Iodine Radioisotopes (therapeutic use)
  • Models, Biological
  • Neuroendocrine Tumors (radiotherapy)
  • Octreotide (analogs & derivatives, pharmacokinetics, therapeutic use)
  • Radiation Dosage
  • Radiopharmaceuticals (pharmacokinetics, therapeutic use)
  • Yttrium Radioisotopes (therapeutic use)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: