PET radiopharmaceuticals beyond 2-[18F]FDG for the evaluation of multiple myeloma and smoldering multiple myeloma

Abstract Purpose This review aims to explore the role of well-established and emerging radiopharmaceuticals different from 2-[ 18 F]FDG (FDG) in multiple myeloma (MM) and smoldering multiple myeloma (SMM), as well as to describe new perspectives in preclinical data. Methods A literature search was performed to identify clinical studies investigating PET radiotracers other than FDG in MM or SMM in the PubMed and Cochrane Library databases. Data were extracted into summary tables, detailing characteristics such as the mechanism of action of each radiopharmaceutical. For future perspectives, clinical studies were retrieved for imaging MM/SMM with radiopharmaceuticals targeting integrins, while preclinical studies were retrieved for those targeting CD-138, VLA-4, anti-BCMA, and nanoparticles. Results A total of 28 clinical studies with the following radiopharmaceuticals: [ 11 C]methionine, [ 18 F]FET, [ 18 F]fluciclovine, [ 11 C]acetate, [ 11 C]choline, [ 18 F]choline, [ 68 Ga]Ga-PSMA-11, [ 18 F]NaF, [ 68 Ga]Ga-DOTATATE, [ 68 Ga]Ga-FAPI-04, [ 68 Ga]Ga-pentixafor and [ 89 Zr]/[ 64 Cu]daratumumab were found and summarized. For future perspectives, one clinical study targeting integrins and four preclinical studies were summarized. Conclusion Compared to FDG, alternative tracers show promise for improved detection. However, their routine clinical use is limited by factors such as availability, cost, and lack of validation in large multicenter studies. Further research, including dual-tracer and theragnostic approaches, is essential but still far from everyday clinical application.