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Objective(s): Miltuximab® is a chimeric antibody targeting Glypican-1 (GPC-1), a cell surface antigen which is overexpressed in solid cancers. Miltuximab® has shown promising safety and efficacy in radioimmunotherapy models of prostate cancer. This first in human study used Miltuximab® radiolabelled with Gallium-67 ([67Ga]Ga-DOTA-Miltuximab®). The primary study endpoint was to establish safety and tolerability of Miltuximab®. Secondary endpoints were biodistribution, tumour targeting and pharmacokinetic analysis. Methods: Four cohorts of three patients (9 with advanced prostate cancer, 2 with pancreatic and 1 with bladder cancer) were dosed with 1 mg, ~250 MBq of [ 67Ga]Ga-DOTA-Miltuximab®. Cohort 1 received [67Ga]Ga-DOTA-Miltuximab® alone, while cohorts 2-4 were pre-infused with increasing doses (3.5, 11.5 and 24 mg, respectively) of unlabelled Miltuximab®-DOTA 1 hour prior to [67Ga]Ga-DOTAMiltuximab®. Safety and tolerability were assessed by clinical and standard laboratory assessments. Patients underwent whole body gamma-camera scans and SPECT/CT scans up to 144 h post-infusion. Total organ radiation exposure was determined by dosimetry of whole-body gamma scans. Results: The dosing regimen was well tolerated, with no drug-related adverse events observed. Liver and spleen uptake of [67Ga]Ga-DOTA-Miltuximab® was observed. Liver uptake was reduced by pre-infusion of unlabelled Miltuximab®- DOTA. Dosimetry analysis showed a favorable exposure profile. [67Ga]Ga-DOTAMiltuximab® targeting to tumour sites was observed in two prostate cancer patients who had failed enzalutamide treatment. Higher doses of unlabelled antibody achieved lower liver uptake and increased antibody serum half life. Conclusions: This study is the first in human for Miltuximab® a first in class antibody targeting GPC-1. The trial met its primary endpoint of safety, demonstrating its potential as a safe and tolerable monoclonal antibody. This safety data, together with targeting to tumour lesions and biodistribution information supports the further clinical development of Miltuximab® as a theranostic agent in a planned Phase I human trial. [ABSTRACT FROM AUTHOR]

A limitation to the wider introduction of personalised dosimetry in theranostics is the relative paucity of imaging radionuclides with suitable physical and chemical properties to be paired with a long-lived therapeutic partner. As most of the betaemitting therapeutic radionuclides emit gamma radiation as well they could potentially be used as the imaging radionuclide as well as the therapeutic radionuclide. However, the downsides are that the beta radiation will deliver a significant radiation dose as part of the treatment planning procedure, and the gamma radiation branching ratio is often quite low. Gallium-67 has been in use in nuclear medicine for over 50 years. However, the tremendous interest in gallium imaging in theranostics in recent times has focused on the PET radionuclide gallium-68. In this article it is suggested that the longer-lived gallium-67, which has desirable characteristics for imaging with the gamma camera and a suitably long half-life to match biological timescales for drug uptake and turnover, has been overlooked, in particular, for treatment planning with radionuclide therapy. Gallium-67 could also allow non-PET facilities to participate in theranostic imaging prior to treatment or for monitoring response after therapy. Gallium-67 could play a niche role in the future development of personalised medicine with theranostics. [ABSTRACT FROM AUTHOR]