Integrin αvβ3 imaging of radioactive iodine-refractory thyroid cancer using 99mTc-3PRGD2.
Integrin α(v)β(3) has been proposed as a potential imaging target for radiolabeled RGD peptides and a molecular marker for the estimation of tumor angiogenesis, yet it has not been applied in differentiated thyroid cancer (DTC) patients with radioactive iodine-refractory (RAIR) lesions. The current study was conducted to assess the potential of integrin α(v)β(3) imaging in the detection of RAIR DTC lesions using (99m)Tc-PEG(4)-E[PEG(4)-c(RGDfK)](2) ((99m)Tc-3PRGD2), thus providing a feasible antiangiogenetic therapeutic target.


METHODS
Ten DTC patients (2 men, 8 women; mean age ± SD, 56.4 ± 9.8 y; age range, 42-73 y) with multiple RAIR metastases were recruited; all patients had both elevated thyroglobulin levels (thyroglobulin-positive) and negative (131)I whole-body scan (WBS) results. Clinical data were collected including history, (131)I WBS, contemporary CT, ultrasonography, thyroid-stimulating hormone, thyroglobulin, and antithyroglobulin. One or 2 target lesions were selected on the contemporary CT images using Response Evaluation Criteria in Solid Tumors 1.0 for all patients, 7 of whom were chosen for the calculation of the rates of lesion growth within the 3 mo before the study. WBS at 30 min and regional SPECT for lesions at 1 h were performed after the intravenous injection of (99m)Tc-3PRGD2. Two experienced nuclear medicine physicians read the images in a masked fashion. The tumor-to-background ratios were calculated for further analysis.


RESULTS
All the target RAIR metastatic lesions were identified as positive on (99m)Tc-3PRGD2 SPECT images. There was a significant correlation between the mean tumor-to-background ratios and mean growth rates of target lesions (r = 0.878, P = 0.009).


CONCLUSIONS
The RAIR ((131)I WBS-negative/thyroglobulin-positive) metastatic lesions can be traced using (99m)Tc-3PRGD2 imaging, meaning these lesions are highly neovascularized. (99m)Tc-3PRGD2 angiogenesis imaging can be used for the localization and growth evaluation of RAIR lesions, providing a new therapeutic target and a novel imaging modality to monitor the efficacy of certain antiangiogenetic therapy.
Department of Nuclear Medicine, Peking Union Medical College Hospital, Beijing, China.
Dan
D
Zhao
Xiaona
X
Jin
Fang
F
Li
Jun
J
Liang
Yansong
Y
Lin
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods*; D009362:Neoplasm Metastasis; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D010456:Peptides, Cyclic / Q000493:pharmacokinetics; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D017211:Treatment Failure
D039302:Integrin alphaVbeta3; D007457:Iodine Radioisotopes; D015609:Organotechnetium Compounds; D010456:Peptides, Cyclic; C561921:technetium 99m (HYNIC-3PRGD(2))(tricine)(TPPTS)