Pilot study of PET imaging of 124I-iodoazomycin galactopyranoside (IAZGP), a putative hypoxia imaging agent, in patients with colorectal cancer and head and neck cancer

Joseph A O'Donoghue, José G Guillem, Heiko Schöder, Nancy Y Lee, Chaitanya R Divgi, Jeannine A Ruby, John L Humm, Steven A Lee-Kong, Eva M Burnazi, Shangde Cai, Sean D Carlin, Tobias Leibold, Pat B Zanzonico, C Clifton Ling, Joseph A O'Donoghue, José G Guillem, Heiko Schöder, Nancy Y Lee, Chaitanya R Divgi, Jeannine A Ruby, John L Humm, Steven A Lee-Kong, Eva M Burnazi, Shangde Cai, Sean D Carlin, Tobias Leibold, Pat B Zanzonico, C Clifton Ling

Abstract

Background: Hypoxia within solid tumors confers radiation resistance and a poorer prognosis. 124I-iodoazomycin galactopyranoside (124I-IAZGP) has shown promise as a hypoxia radiotracer in animal models. We performed a clinical study to evaluate the safety, biodistribution, and imaging characteristics of 124I-IAZGP in patients with advanced colorectal cancer and head and neck cancer using serial positron emission tomography (PET) imaging.

Methods: Ten patients underwent serial whole-torso (head/neck to pelvis) PET imaging together with multiple whole-body counts and blood sampling. These data were used to generate absorbed dose estimates to normal tissues for 124I-IAZGP. Tumors were scored as either positive or negative for 124I-IAZGP uptake.

Results: There were no clinical toxicities or adverse effects associated with 124I-IAZGP administration. Clearance from the whole body and blood was rapid, primarily via the urinary tract, with no focal uptake in any parenchymal organ. The tissues receiving the highest absorbed doses were the mucosal walls of the urinary bladder and the intestinal tract, in particular the lower large intestine. All 124I-IAZGP PET scans were interpreted as negative for tumor uptake.

Conclusions: It is safe to administer 124I-IAZGP to human subjects. However, there was insufficient tumor uptake to support a clinical role for 124I-IAZGP PET in colorectal cancer and head and neck cancer patients.

Trial registration: ClinicalTrials.gov NCT00588276.

Figures

Figure 1
Figure 1
PET/CT images of 18F-FDG and 124I-IAZGP in a rectal cancer patient. (A to D) Coronal maximum intensity projection PET images of 18F-FDG acquired 3 days before 124I-IAZGP administration (A) and 124I-IAZGP acquired at 3 h (B), 6 h (C), and 25 h (D) post-administration in a patient with primary rectal cancer with liver metastases. (E to G) Cross-sectional fused PET/CT images of the same patient comparing 18F-FDG (E and F left, G top) with 124I-IAZGP at 3 h (E and F right, G bottom). No evidence of 124I-IAZGP uptake is seen in either FDG-avid primary or metastatic lesions. The 124I-IAZGP MIP images (B to D) also illustrate the characteristic pattern of 124I-IAZGP clearance, initially via the urinary tract with longer term excretion via the GI tract. Note that image intensities are not directly comparable as window levels were adjusted to maximize feature visibility.
Figure 2
Figure 2
PET/CT images of 18F-FDG and 124I-IAZGP in a head and neck cancer patient. (A to D) Coronal maximum intensity projection PET images of 18F-FDG acquired 3 days before 124I-IAZGP administration (A) and 124I-IAZGP acquired at 3 h (B), 6 h (C), and 27 h (D) post-administration in a patient with head and neck cancer. (E to G) Cross-sectional fused PET/CT images of the same patient comparing 18 F-FDG (E and F left, G top) with 124I-IAZGP at 6 h (E and F right, G bottom). No evidence of 124I-IAZGP uptake is seen in either the FDG-avid supraglottic larynx cancer or the approximately 2-cm lymph node. The clearance of 124I-IAZGP is similar to that seen in Figure 1, with a symmetric distribution of physiologic 124I in the salivary glands. Note that image intensities are not directly comparable and that the 18F-FDG image was acquired in the radiotherapy treatment position with the patient in a facial mask.

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