The MEGHAN trial was a randomized phase II study that evaluated drug efficacy of MEHD7945A compared to cetuximab in patients with recurrent/metastatic squamous cell carcinoma of the head and neck that progressed after chemotherapy26. Compared to cetuximab treatment alone, the study found that MEHD7945A did not significantly improve patient outcomes, even those with amplified neuregulin-1 expression, a HER3 ligand, as measured by disease free survival26. Despite this dismal outcome, the combined blockade of EGFR and HER3 merits a second look with trials that particularly focus on EGFR treatment-resistant patient populations. This rationale stems from an overwhelming body of evidence showing that dual inhibition of EGFR and HER3 promotes desensitization of lesions to EGFR blockade through HER3 crosstalk inhibition27–29. With this perspective, our initiative to develop a companion diagnostic to MEHD7945A is potentially useful for selecting patients within this space in order to benefit from this treatment. To the best of our knowledge, we are the first to develop a new PET radiotracer that simultaneously delineates both of EGFR and HER3 receptors. Only one recent study has described a bi-specific immunoPET imaging tracer, albeit, of different receptors, CD3 and EpCAM30. Other previous and currently investigated immunoPET tracers specific to these two receptor tyrosine kinases are limited to single antigen detection with either EGFR25,31–33 or HER334–37 alone. The paradigm is shifting, however, to combinatorial drug cocktails to debulk tumor. The quest for a potent and efficient therapy led to the development of bispecific antibodies or fragments to target more than one molecular signature (tumor associated antigens) amplified in lesions, e.g., EGFR/IGF1-R38, EGFR/Met39, and HER2/HER340. This stems from the rationale that a single agent targeting multiple markers vis-à-vis a monospecific approach can strongly stabilize specificity and selectivity for tumor instead of normal tissues. To select a patient population who stands to benefit from the treatment, non-invasive and quantitative imaging biomarkers are of utmost need. We believe that 89Zr-MEHD7945A satisfies this initiative.