Preface Free

Radiopharmaceuticals represent a unique class of pharmaceuticals, capable of being used to both diagnose and treat a range of diseases. With origins that can be traced back to the 1920s and 1930s, radiopharmaceuticals have evolved significantly, becoming integral to modern medicine. They offer healthcare professionals the remarkable ability to visualize and target diseases non-invasively. Early radiopharmaceuticals were primarily diagnostic, relying on isotopes such as metastable technetium-99 (technetium-99m), fluorine-18, and iodine-131, vital for therapeutic applications. Today, the advent of theragnostic pairs like gallium-68–lutetium-177 has transformed this field, fostering the development of targeted theragnostic radiopharmaceuticals. Over the past decade, the radiopharmaceutical industry has attracted substantial investments from major pharmaceutical and biotech companies, signaling the growing importance of radiopharmaceuticals in clinical settings.

Historically, radionuclide therapies were considered a palliative, last-resort option. However, the success of landmark trials like Neuroendocrine Tumors Therapy (NETTER) and VISION, followed by the United States Food and Drug Administration (FDA) approval of [¹⁷⁷Lu]Lu-dodecane tetraacetic acid–tyrosine-3-octreotate (DOTA–TATE) (Lutathera®) and [¹⁷⁷Lu]Lu-dodecane tetraacetic acid–prostate-specific membrane antigen inhibitor 617(DOTA–PSMA-617) (Pluvicto®), has reshaped this perception. Additionally, the approval of [²²³Ra]RaCl₂ (Xofigo®), the first FDA-approved alpha emitter, has paved the way for targeted alpha therapies. Initial clinical results using ²²⁵Ac-labeled DOTA–TATE and DOTA–PSMA-617 have shown promising responses, even in patients unresponsive to ¹⁷⁷Lu-based therapies. What was once considered futuristic—targeted radionuclide therapies tailored to specific diseases—has become a reality, offering more precise, personalized, and effective treatments.

The bench-to-bedside development of radiopharmaceuticals and further commercialisation and distribution involves multiple stages. This aim of this book is to provide a comprehensive overview of the various aspects of radiopharmaceutical development, including chemistry, dosimetry, commercialization, and the latest advancements. It addresses the critical challenges in the field and offers a broad perspective on the technologies shaping the future of targeted radiopharmaceuticals and imaging. The chapters in this book cover a wide array of topics:

• A basic introduction to radiopharmaceuticals, along with developmental and commercialisation details of recently FDA-approved therapeutic radiopharmaceuticals. Challenges associated with developing therapeutic radiopharmaceuticals, especially alpha emitters, recent advancements, and dosimetry are also explored.

• Insights into the process of identifying newer molecular targets for developing radiopharmaceuticals, with real-world examples of the stages a radiopharmaceutical undergoes during development. The focus extends to peptide-based, small-molecule, and protein-based radiopharmaceuticals, highlighting their distribution and clinical applications.

• Detailed discussion of the wide applications of diagnostic and therapeutic radiopharmaceuticals in oncological and non-oncological conditions, emphasizing specific radiopharmaceuticals’ pharmacokinetics, clinical use, and advancements.

• In-depth coverage of the chemistry of fluorine-18-based radiopharmaceuticals, the development of metallic radiopharmaceuticals, and the challenges of manufacturing. Chapters describe essential aspects of manufacturing and quality control in the development and routine synthesis of radiopharmaceuticals.

The contributors to this book are leading experts from prominent research institutes worldwide, including the Tri-University Meson Facility (TRIUMF), Canada, the Mayo Clinic’s Comprehensive Cancer Center, Johns Hopkins University, Tata Memorial Centre (TMC), All India Institute of Medical Sciences (AIIMS), and Postgraduate Institute of Medical Education and Research (PGIMER). We are deeply grateful to the contributing authors for sharing their valuable expertise and insights with the broader scientific and medical communities. The following is a full list of the contributing authors and their affiliations.

• Aarti Aggarwal PhD, Postgraduate Institute of Medical Education and Research, Department of Nuclear Medicine, Chandigarh, India

• Adam Mezo PhD, Neurocrine Biosciences, San Diego, CA, USA

• Anjugam Alagappan MD, DNB, Arunai Medical College and Hospital, Tiruvannamalai, Tamil Nadu, India

• Anupriya Chhabra PhD, Johns Hopkins University, School of Medicine, Baltimore, USA

• Ashish Kumar Jha PhD, Tata Memorial Hospital, Mumbai, India

• Ashwani Sood DRM, DNB, Professor, Postgraduate Institute of Medical Education and Research, Chandigarh, India

• Bhagwant Rai Mittal MD, DRM, DNB, Professor and Head, Postgraduate Institute of Medical Education and Research, Chandigarh, India

• Bhakti Shetye MSc, Tata Memorial Hospital, Parel, Mumbai, India

• Deborah Charych PhD, Utter Therapeutics, San Francisco, CA, USA

• Esha Agarwal MS, University of North Carolina, NC, USA

• Farhad Golmohammadi MSc, Peptide Chemistry Research Institute, K. N. Toosi University of Technology, Tehran, Iran

• Greg Chen PhD, US Rad Bio, San Diego, CA, USA

• Gurvinder Kaur PhD, Postgraduate Institute of Medical Education and Research, Chandigarh, India

• Harmandeep Singh MD, Postgraduate Institute of Medical Education and Research, Chandigarh, India

• Helena Koniar PhD, Life Science Division, TRIUMF, Vancouver, BC, Canada

• Jaya Shukla PhD, Professor, Postgraduate Institute of Medical Education and Research, Chandigarh, India

• Junise Moideen MD, FRANZCR, Townsville University Hospital, Queensland, Australia

• Kanhaiyalal Aggarwal MD, All India Institute of Medical Sciences, Bhubaneshwar, Odisha, India

• Karan Singh Tanwar MSc, Tata Memorial Centre, Advanced Centre for Treatment, Research, and Education in Cancer, Navi Mumbai, India

• Kinnari Chitnis MSc, Tata Memorial Hospital, Parel, Mumbai, India

• Kiruthika Subburaj MD, DNB, Dharan Hospital and Cancer Specialty Centre, Salem, Tamil Nadu, India

• Komalpreet Kaur MSc, Postgraduate Institute of Medical Education and Research, Chandigarh, India

• M. Ganesh Kumar MD, Kiran Multi Superspeciality Hospital, Surat, India

• Mukesh Pandey PhD, Professor, Mayo Clinic Comprehensive Cancer Center, Rochester, MN, USA

• Mythili Kameswaran PhD, Tata Memorial Hospital, Parel, Mumbai, India

• Navneet Kumar MSc, All India Institute of Medical Sciences, Bhubaneshwar, Odisha, India

• Nivedita Rana PhD, Postgraduate Institute of Medical Education and Research, Chandigarh, India

• Paul Schaffer PhD, Director, Life Science Division, TRIUMF, Vancouver, BC, Canada

• Piyush Aggarwal MD, Postgraduate Institute of Medical Education and Research, Chandigarh, India

• Punit Sharma MD, Apollo Multispeciality Hospital, Kolkata, West Bengal, India

• Rakhee Vatsa PhD, Tata Memorial Centre, Advanced Centre for Treatment, Research, and Education in Cancer, Navi Mumbai, India

• Rongjun He PhD, Neurocrine Biosciences, San Diego, CA, USA

• Saeed Balalaie PhD, Professor, Peptide Chemistry Research Institute, K. N. Toosi University of Technology, Tehran, Iran

• Sayak Choudhury MD, Tata Memorial Centre, Advanced Centre for Treatment, Research, and Education in Cancer, Navi Mumbai, India

• Sejal Chopra MSc, Postgraduate Institute of Medical Education and Research, Chandigarh, India

• Shashank Shekhar Singh DNB, Globe Healthcare, Lucknow, India

• Shelvin Kumar Vadi MD, Baby Memorial Hospital, Calicut, India

• Sneha Mithun PhD, Tata Memorial Hospital, Parel, Mumbai, India

• Somit Pandey PhD, Postgraduate Institute of Medical Education and Research, Chandigarh, India

• Suchismita Ghosh MD, Tata Memorial Centre, Advanced Centre for Treatment, Research, and Education in Cancer, Navi Mumbai, India

• Tejasvini Singhal MD, All India Institute of Medical Sciences, Bhubaneshwar, Odisha, India

• Thomas Harding PhD, Utter Therapeutics, San Francisco, CA, USA

• Vaezeh Fathi Vavsari PhD, Peptide Chemistry Research Institute, K. N. Toosi University of Technology, Tehran, Iran

• Ved Srivastava PhD, Perpetual Medicines, Raleigh, NC, USA

• Venkata Subramanian Krishnaraju MD, DNB, Dharan Hospital and Cancer Specialty Centre, Salem, Tamil Nadu, India

• Venkatesh Rangarajan DRM, DNB, Professor, Tata Memorial Hospital, Parel, Mumbai, India

• Viktoria Krol PhD, Mayo Clinic, Rochester MN, USA

This book will be an indispensable resource for radiopharmaceutical researchers, pharmaceutical scientists, graduate and postgraduate students, and medical professionals. It will also provide valuable insights for chemists and other professionals involved in drug discovery, development, biotechnology, and radiopharmaceutical manufacturing in both academic and industry settings.

Ved Srivastava and Rakhee Vatsa