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Dosimetric Comparison of the Hypoxia Agent Iodoazomycin Arabinoside (IAZA) Labeled with the Radioisotopes I-123, I-131 and I-124

H Jans

H-S Jans^1,2*, D Stypinski³ , S Mcquarrie², P Kumar², J Mercer² , L Wiebe¹ , S McEwan², (1) Cross Cancer Institute, Edmonton, AB, Canada(2) Dept. of Oncology, University of Alberta, Edmonton, AB, Canada (3) Celerion Inc., Lincoln, NE

Presentations

SU-E-CAMPUS-I-3 Sunday 3:00PM - 6:00PM Room: Exhibit Hall

Purpose: To compare the radiation dose to normal organs from the radio-iodinated, hypoxia-binding radiosensitizer iodoazomycin arabinoside (IAZA) for three different isotopes of iodine.

Methods: Dosimety studies with normal volunteers had been carried out with [¹²³I]IAZA, a drug binding selectively to hypoxic sites. Two other isotopes of iodine, ¹³¹I and ¹²⁴I, offer the opportunity to use IAZA as an agent for radioisotope therapy and as an imaging tracer for Positron Emission Tomography. Radioisotope dosimetry for ¹³¹I and ¹²⁴I was performed by first deriving from the [¹²³I]IAZA studies biological uptake and excretion data. The cumulated activities for ¹³¹I or ¹²⁴I where obtained by including their half-lives when integrating the biological data and then extrapolating to infinite time points considering a) physical decay only or b) physical and biological excretion. Doses were calculated using the Medical Internal Radiation Dose (MIRD) schema (OLINDA1.1 code, Vanderbilt 2007).

Results: Compared to ¹²³I, organ doses were elevated on average by a factor 6 and 9 for ¹³¹I and ¹²⁴I, respectively, if both physical decay and biological excretion were modeled. If only physical decay is considered, doses increase by a factor 18 (¹³¹I) and 19 (¹²⁴I). Highest organ doses were observed in intestinal walls, urinary bladder and thyroid. Effective doses increased by a factor 11 and 14 for ¹³¹I and ¹²⁴I , respectively, if biological and physical decay are present. Purely physical decay yields a 23-fold increase over ¹²³I for both, ¹³¹I and ¹²⁴I.

Conclusion: Owing to the significant dose increase, caused by their longer half life and the approximately 10 times larger electronic dose deposited in tissue per nuclear decay, normal tissue doses of IAZA labeled with ¹³¹I and ¹²⁴I need to be carefully considered when designing imaging and therapy protocols for clinical trials. Effective blocking of iodine uptake in the thyroid is essential.

Funding Support, Disclosures, and Conflict of Interest: Alberta Innovates - Health Solutions (AIHS) and Canadian Institutes of Health Research (CIHR)


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