Researchers at the 2016 Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) presented a molecular imaging methodology that allows the increase of the radiotherapy dose to the tumor while protecting vulnerable vital organs.¹

The delicate balance of administering the maximum safe dose—better known as personalized dosimetry—can vary widely between patients. A number of radiotherapies that marry a radioactive material and a targeted molecular compound have been gaining traction as progressive treatments for malignant neuroendocrine tumors.

We expect better outcomes in radionuclide therapy with fewer complications, because we will be able to adjust patient dose either up or down as needed.

— Mark T. Madsen, PhD

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Scientists are taking preemptive action by using already available molecular imaging systems to determine the optimal dose of the molecular targeted radiotherapy agent yttrium-90 DOTA0-Tyr3-octreotide (Y-90 DOTATOC). “DOTATOC is a peptide that binds with somatostatin receptors that are often highly expressed in neuroendocrine cancers,” said Mark T. Madsen, PhD, Professor of Radiology at the University of Iowa Carver College of Medicine, Iowa City. “With molecular imaging, we are able to see whether the DOTATOC imaging agent is taken up by the tumor. If it is, we know that the Y-90 DOTATOC radiotherapy will also reach the tumor and be able to kill tumor cells.”

The objective here is to set the bar for the highest possible therapeutic radiation dose to neuroendocrine tumors that does not exceed toxic radiation levels to the kidneys, which take the brunt of the residual drug that does not bind to its targets. Results of this research have shown that use of positron-emission tomography (PET) and single-photon–emission computed tomography (SPECT), which image physiologic functions of the body such as peptide receptor activity, led to dramatically altered dosimetry in all participating patients.

Personalized Dosimetry

For this study, researchers worked with 12 patients with malignant neuroendocrine tumors to find an adaptive approach to personalized dosimetry during three cycles of radiotherapy. All adult patients underwent 4.44 GBq of Y-90 DOTATOC, and pediatric patients received 1.85 GBq/m² during the first course of treatment. Patients were also given an infusion of amino acids as a protective measure against kidney toxicity.

The researchers evaluated blood and renal dosimetry after the first and second courses of radiotherapy to discern the best possible dose of Y-90 DOTATOC for successive courses. Dosimetry was performed by imaging patients with quantitative PET/computed tomography (CT) about 5 hours after administration of Y-90 DOTATOC, followed by quantitative SPECT/CT imaging. SPECT/CT imaging was also repeated at 24-, 48-, and 72-hour intervals after injection. Y-90 burden and kidney mass were determined from reconstructed PET and CT images.

Marked Changes in Dosing

The investigators were able to complete 20 dosimetry evaluations for the 12 patients involved in the study. Y-90–activity accumulation in the kidneys ranged from 1.4% to 3.6%. The kidney dose ranged from 0.6 to 2.7 mGy/MBq, and the blood dose ranged from 0.04 to 0.24 mGy/MBq. These findings led to marked changes in subsequent cycles of treatment. The dose of radiotherapy was not increased for two injections in children, and one patient’s treatment ended after only one course of treatment. For the others, the dose of radiotherapy was increased in eight courses and decreased in three courses. Overall, the prescribed dose of radiotherapy was altered by more than 15% in a total of 11 courses of radiotherapy.

“Our approach combines the advantages of quantitative Y-90 PET and SPECT imaging to gather all the information required to accurately estimate kidney dose,” said Dr. Madsen. “We expect better outcomes in radionuclide therapy with fewer complications, because we will be able to adjust patient dose either up or down as needed.”

Although this method of personalized dosimetry was used to determine the maximum dose that is safe for the kidneys, this imaging technique could be equally used to determine the most effective dose to combat neuroendocrine tumors. Further studies should elucidate how best to apply this technique. ■

Disclosure: Dr. Madsen reported no potential conflicts of interest.

Reference

1. Madsen MT, Menda Y, Sunderland JJ, et al: 2016 Society of Nuclear Medicine and Molecular Imaging Annual Meeting. ­Abstract 582.