Radiolabeled PTP Derivative for Pre- and Intraoperative Mapping of Lymph Nodes by SPECT/Optical Dual-Modality Imaging

Objectives The poly (thiophene) copolymer (PTP) is a member of water-soluble conjugated polymers family with excellent light-harvesting and light-amplifying properties which are determined by their π-conjugated backbones. Owing to the excellent photostability, high fluorescence brightness, remarkable biocompatibility and easy modification, PTP is becoming a class of promising fluorescence probes in biological fields. In this work we firstly designed and synthesized multifunctional probe 99mTc-PTP and used it for lymph nodes detection and dissection based on SPECT/optical dual-modality imaging.

Methods PTP was conjugated with 6-hydrazinonicotinyl (HYNIC) and then radiolabeled with 99mTc. 99mTc-PTP was injected intradermally into the left paw of female BALB/c nude nude mice (n=6). SPECT/CT imaging was obtained at 0.5, 1, 2, 4, 8, 12 and 24 h post injection. The regions of interest were drawn in the forepaw and lymph nodes, and uptake values from 0.5 to 24 h were obtained from a quantitative analysis. Fluorescence imaging was performed 1 h after intradermal injection of 99mTc-PTP/ indocyanine green (ICG) mixture followed by lymph nodes dissection under intraoperative optical imaging guidance. The Acute toxicity test was also performed to evaluate the in vivo safety.

Results 99mTc-PTP was obtained with high radiochemical purity (>98%) after purification. The accumulation of 99mTc-PTP in axillary and lateral thoracic nodes could be clearly detected by SPECT/CT imaging at 0.5 h p.i. The uptake values in the adjacent nodes accumulated from 0.5 h to 4 h and began to decline until 24 h. For axillary node, the uptake values were 3.19, 14.30 and 10.41 ID% at 0.5, 4, and 24 h, respectively. For adjacent node, the uptake values at 0.5, 4, and 24 h were 0.72, 5.35, and 3.34 ID%. The optical signal of 99mTc-PTP could be visualized in lymph nodes and lymphadenectomy was performed at 1 h p.i. The optical signal highly coincided with ICG which confirmed the detection and dissection accuracy. No significant difference was observed in both body weight and blood routine tests even at a high chemometry injection of 99mTc-PTP.

Conclusions Dual-modal probe 99mTc-PTP could successfully monitor SPECT/optical imaging guidance for lymph nodes detection and dissection. The intrinsic light-amplifying properties good photostability as well as excellent biocompatibility make it a promising probe for lymph nodes mapping in clinical applications.

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