Small animal PET studies were carried out 72 h after application of radioconjugates regarding the highest enrichment of the mAbs in the tumors at this time point. All scans were performed in head-first-prone position in a PET-MRI 1T scanner. In some experiments MRI measurements (Material Map) were first performed for co-registration of the PET scan (3D Gradient Echo External Averaging (GRE-EXT), Multi Field of View (FOV); slice thickness: 0,6 mm; TE: 2 ms; TR: 15 ms; flip angle: 25 deg) followed by a static PET scan (collecting 20 million events). PET data were reconstructed with Teratomo 3D (4 iterations, 6 subsets, voxel size 0.4 mm), co-registered to the MR and analyzed with PMOD software (version 3.6, PMOD Technologies LLC).
Figure 5C. shows PET imaging after 72 hours demonstrated a strong accumulation of [⁸⁹Zr]Zr-Df'-GGSK-1/30 in the tumor. The highest amount of [⁸⁹Zr]Zr-Df'-GGSK-1/30 was detected after 72 hours in the tumor (>55 %ID/g). Uptake values in other tissues (lung, heart, spleen, pancreas, stomach, intestines, kidneys, lymph nodes, mammary glands, muscle) were below 20 %ID/g(tissue). The concentration of the [⁸⁹Zr]Zr-Df'-GGSK-1/30 in blood decreased steadily while increasing amounts of [⁸⁹Zr]Zr-Df'-GGSK-1/30 accumulated in the tumor. The radioconjugate showed predominant hepatobiliary excretion with increasing uptake values over time from 22 to 38 %ID/g (liver). The uptake values in bone tissues steadily increased due to the slight degradation of the Zr-Df'-complex in vivo, which is known for ⁸⁹Zr-radiolabeled Df'-conjugated antibodies. An exact calculation of the tumor-to-tissue ratio revealed a comparatively high tumor accumulation.

Figure 6C. shows Selective binding of [⁸⁹Zr]Zr-Df'-GGSK-1/30 to hu(TA)MUC1 expressed by PyMTxhuMUC1 tumors. HuMUC1-transgenic mice bearing a PyMTxhuMUC1 breast tumor transplant subcutaneously on the right flank were treated i.p. with [⁸⁹Zr]Zr-Df'-GGSK-1/30 (80 µg, 2.5 MBq) - left image -, previously saturated with 1200 molar excess of the corresponding glycopeptide: [⁸⁹Zr]Zr-Df'-GGSK-1/30 blocked (50 µg, 0,46 MBq) - right image -:

• Hu(TA)MUC1 is a tumor-specific antigen on breast cancer cells with an exceptionally high diagnostic and potential prognostic value/importance. The radiolabeled derivative [⁸⁹Zr]Zr-Df'-GGSK-1/30 demonstrated high in vivo stability and highly selective and tumor-specific accumulation which resulted in high contrast PET imaging. Thus, GGSK-1/30 represents a promising PET-tracer for clinical studies on molecular imaging in early diagnosis and/or in therapy-accompanying control examinations of breast cancer patients undergoing systemic therapies.
• The mAb GGSK-1/30 represents a platform, which can be used (i) as a diagnostic tool for the detection of hu(TA)MUC1 in early breast cancer diagnosis, (ii) as a prognostic biomarker, (iii) as a companion diagnostic during therapy and (iv) in future perspective in radioimmunotherapy.

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