Editorial for the Research Topic Women in Science – Nuclear Medicine 2024

Bianca Gutfilen¹Marigdalia K Ramirez-Fort, MD^2*

• ¹Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
• ²BioFort, Guaynabo, Puerto Rico

Women are underrepresented in science, particularly at the graduate, postgraduate and faculty level (1). In 2022, women accounted for only 31% of all researchers, globally; the only regions approaching gender parity, was in Latin America and the in the Caribbean (2). Ross et al. further demonstrated that women are systematically under-credited and marginalized, as compared to men, for their scientific aptitude and contributions (3). Women are less likely to be named as authors on scientific papers or to receive credit as named inventors on inventions or patents, when compared to their male colleagues. Qualitative data, (e.g., interviews, surveys, etc.), further supports a misrepresentation of the contribution of women in science and medicine (3). A known example of this misrepresentation is the story of Rosalind Franklin's who took the first radiographic photos of DNA that confirmed that DNA had two helices. Franklin elucidated the anlagen of James Watson and Francis Crick's discovery that DNA was a double-helix polymer, but was never credited for her participation in the discovery of the DNA structure. Another example of the gender disparity described by Ross et al. was recently documented in the United States Federal Court for the District of Puerto Rico (Case No. 3:19-cv-1631). As a resident physician training in a Radiation Oncology residency program, a woman physician-scientist was subjectively labeled as academically deficient compared to her male colleagues. Soon thereafter, she informed her residency supervisor that she had a first-author manuscript, in press, in the International Journal of Radiation Oncology Biology and Physics (4). The residency competency committee then labeled her as having delusions of grandeur, presumably because it was incredulous that a woman resident could accomplish this. The Radiation Oncology faculty then moved to remove her from the residency training program, despite objective measures of academic competency (5, 6, 7). Maria Skłodowska-Curie made it clear that women can play a crucial role in the development and advancement of Radiation Sciences, particularly in Nuclear Medicine. In fact, several women have so-called, 'paved the way', in the pioneering of Radiation Science and Nuclear Medicine. Edith Quimby elucidated how to optimize the radiotherapeutic-index. Irene Joliot-Curie co-discovered that radioactive elements can be artificially produced from stable elements. Rosalyn Sussman Yalow developed the radioimmunoassay technique. Chien-Shiung Wu, disproved "the law of conservation of parity", by discovering that cobalt-60 particle emission is asymmetrical. Tikvah Alper identified the infectious agent in Scrapie; by irradiating scrapie samples with different wavelengths of UV light, Alper was able to prove the infectious agent could replicate despite having no nucleic acid. In 2020, a mother-daughter research team, published their inventive methods for cellular-level dosimetry for radiopharmaceuticals (8). It is essential to acknowledge that women in Nuclear Medicine, encounter gender-based challenges and obstacles in the battle to be recognized for their intellectual contributions. Still, women continually demonstrate competence, dedication, and excellence in their professional practices. This Research Topic aimed to create opportunities to recognize and to honor the recent contributions of women in Nuclear Medicine, while also promoting gender equality. Hu H et al. developed 131I-labeled HER2 affibodies as targeted radionuclide therapy agents (TRNT) for HER2-positive ovarian carcinoma. The YZHER2:v2 affibody targeting HER2 was synthesized through genetic recombination. Radiopharmaceutical tumor accumulation, retention, and advantageous distribution were observed in mice with HER2-positive tumors. Mice treated with 131I-YZHER2:v2 showed reduced tumor growth and prolonged survival (9). Sharing information on techniques for developing novel radiopharmaceuticals to target a variety of known proteins expressed by cancers, is fundamental towards optimizing radiation dose delivery to disseminated cancers. In an Opinion article, Ramirez-Fort et al. draw attention to the fact that the use of gender-and disease-exclusive language in science and medicine can lead to the exclusion of patients, particularly genotypic women, from important diagnostic and therapeutic opportunities. One example is the term "prostate-specific membrane antigen" (PSMA), widely used in oncology. The PSMA protein is encoded by the FOLH1 gene, is present in all human solid tumors. Maintaining the term "PSMA" perpetuates a gendered view and a false exclusive association with prostate cancer. On March 28, 2025, the United States Federal Drug Administration (FDA) expanded its indication for a "PSMA"- Targeted radiopharmaceutical within the scope of treating metastatic prostate cancer only. The FDA's indications for a misnamed radiopharmaceutical, forms the basis for Centers for Medicare and Medicaid reimbursement. As the authors express that since it has been known for decades, that "PSMA" is expressed within the lumen of all cancer neovessels, standardizing protein nomenclature from PSMA to FOLH1 is the first important step towards achieving gender equality in opportunities for use of PSMA-targeted radiopharmaceuticals (10)(11). Focusing on future clinical applications, Burgard C et al. aimed to identify suitable prognostic dynamic parameters derived from baseline and follow-up [18F] FDG PET/CT, as well as dual-tracer imaging PET/CT, for monitoring metastatic castrate resistant prostate cancer (mCRPC) patients who are not responding to PSMA-targeted therapy. They identify a novel biomarker called "change of glucometabolic activity per PSMA expression for total lesions" (cGAPTL) that is a normalized ratio of whole-body lesion glycolysis to whole-body lesion PSMA. Importantly, cGAPTL is shown to reliably predict overall survival in mCRPC patients who did not respond to [177Lu] Lu-PSMA-617 radioligand therapy (12). It will be exciting to see how cGAPTL may aid in optimizing radiopharmaceutical treatment planning of disseminated prostate cancer. In Original Research, Peretti et al., describes the prevalence of PET and MRI-quantified ATN profiles of two separate patient cohorts to determine neuroimaging-based ATN profiles are standardizable. Currently, Alzheimer's disease is staged by level of neurodegeneration (N) and is histopathologically diagnosed based on amyloid (A) plaques and neurofibrillary tau (T) tangles. Together, these parameters form the ATN classification system for potential use as a standardized method for evaluating disease progression within clinical trials or efficacy of new drugs. This study shows that neuroimaging alone establishes reproducible and consistent ATN profiling amongst centers with different clinical cohorts and imaging protocols (13). The undersigned Volume Editors conclude that the authors of this special issue for Women in Science have made important intelectual contributions to Nuclear Medicine.