Case Report: Gangrene after one dose of investigational stannic pentetate radiopharmaceutical

IntroductionBone-seeking radiopharmaceuticals are the treatment of choice with clinical benefits for patients with extensive skeletal metastases, but they can also cause serious radiation-related adverse events (rrAEs). Management of rare and severe radiopharmaceutical rrAEs remains challenging because of incomplete knowledge of their natural history and pathogenetic mechanisms. We report a case of unlikely related gangrene following a protracted hospitalization after one dose of investigational [117mSn]tin-117m-diethylenetriaminepentaacetic acid (Sn-117m-DTPA) for treatment of extensive skeletal metastases from castration-resistant prostate cancer (mCRPC).Case presentationAn 80-year-old man with innumerable painful skeletal metastases from mCRPC developed anorexia and bilateral ankle edema with serous-draining skin fissures of the left foot, worrisome for uninfected dry gangrene, 24 days after receiving a single administration of Sn-117m-DTPA (710 MBq) in a phase II clinical trial (NCT04616547). Laboratory investigations revealed leukopenia (3,180 ml−1). Thirteen days later (cycle 1, day 37), he reported anorexia, chills, and generalized weakness, and also had bilateral pedal gangrene. Emergent left above-the-knee amputation and right transphalangeal (ray 2) amputation revealed tissue necrosis complicated by blistering and foul-smelling discharge. He developed postsurgical respiratory decompensation requiring intubation, vasopressors, and broad-spectrum antibiotics. Despite escalating supportive care and enteral feeding, only limited improvement was observed during hospitalization lasting more than 1 month. Five weeks after the onset of pedal gangrene, the patient succumbed to sepsis attributed to a methicillin-sensitive Staphylococcus aureus aspiration pneumonia. No autopsy was performed. Remarkably, prior to these events and at sites of skeletal metastases from mCRPC, he reported a substantial reduction in pain (from a score of 7 to 3 on an 11-point scale) and reduced use of oral narcotic analgesia (from three to two times daily).ConclusionGangrene, complicated by leukopenia and sepsis from aspiration pneumonia, is a rarely reported serious adverse event occurring late after a radiopharmaceutical treatment. Given that the window of reversibility for gangrene is narrow, prompt and decisive intervention is warranted. Subtle perturbations in skin integrity after radiopharmaceutical treatment may be more prevalent than realized and should be addressed in both clinical and investigational settings.