Radiotheranostics in Cancer Diagnosis and Management

Abstract

The fundamental foundation for precision medicine is accurate and specific targeting of cancer cells. Advances in the understanding of cancer biology, developments in diagnostic technologies, and expansion of therapeutic options have all contributed to the concept of personalized cancer care. Theranostics is the systematic integration of targeted diagnostics and therapeutics. The theranostic platform includes an imaging component that "sees" the lesions followed by administration of the companion therapy agent that "treats" the same lesions. This strategy leads to enhanced therapy efficacy, manageable adverse events, improved patient outcome, and lower overall costs. Radiotheranostics refers to the use of radionuclides for the paired imaging and therapy agents. Radioiodine is the classic radiotheranostic agent that has been used clinically in management of thyroid diseases for nearly 75 years. More recently there have been major exciting strides in radiotheranostics for neuroendocrine tumors and prostate cancer, among other conditions. Regulatory approval of a number of radiotheranostic pairs is anticipated in the near future. Continued support will be needed in research and development to keep pace with the current momentum in radiotheranostics innovations. Moreover, regulatory and reimbursement agencies need to streamline their requirements for seamless transfer of the radiotheranostic agents from the bench to the bedside. In this review, the concept, history, recent developments, current challenges, and outlook for radiotheranostics in the treatment of patients with cancer will be discussed. ^© RSNA, 2018.

Figure 1:

Schematic of the human sodium iodide symporter with 13 transmembrane domains, an extracellular NH₂ terminus, and a cystosolic COOH terminus. (Reprinted, with permission, from reference .)

Figure 2:

Negative ¹³¹I whole-body planar scan (left) and positive fluorodeoxyglucose (FDG) PET scan (right) in a patient after thyroidectomy and suspected of having recurrent thyroid carcinoma based on elevated serum thyroglobulin level. Physiologic radioiodine accumulation is noted in the nasal mucosa, salivary glands, stomach, and urinary bladder in the ¹³¹I whole-body planar scan. FDG PET scan demonstrates metabolically active metastatic right cervical adenopathy. (Reprinted, with permission, from reference .)

Figure 3:

Intraindividual comparison of ¹¹¹In-octreo/ide scintigraphy performed 24 hours after tracer administration and ⁶⁸Ga-DOTATATE PET performed 1 hour after tracer administration. Note the marked improvement in localization of tumor foci with ⁶⁸Ga-DOTATATE. (Image courtesy of Andrei Iagaru, MD, Stanford University.)

Figure 4:

Graphs shows markedly improved progression-free and overall survival in patients with midgut neuroendocrine tumors receiving ¹⁷⁷Lu-DOTATATE relative to control group. (Reprinted, with permission, from reference .)

Figure 5:

Schematic of prostate-specific membrane antigen consisting of a short NH₂-terminal cytoplasmic domain (CD, amino acids 1–19), a transmembrane domain (TM, amino acids 20–44), and a large extracellular domain (ED, amino acids 45–750). Letters A-G refer to various subdomains and Y represents N-glycosylation sites. (Reprinted, with permission, from reference .)

Figure 6:

⁶⁸Ga-PSMA PET scans at, A, baseline, and B–D, after respective cycles of targeted radionuclide therapy in a patient with extensive castration-resistant metastatic cancer who was initially treated unsuccessfully with two cycles ¹⁷⁷Lu-PSMA-617 (beta-particle therapy) and subsequently treated successfully with total of three cycles of ²²⁵Ac-PSMA-617 (alpha-particle therapy). The dates of PET scans and serum prostate-specific antigen levels (PSA) are at the bottom of each image. (Reprinted, with permission, from reference .)

Figure 7:

A, ⁶⁸Ga-pentixafor and fluorodeoxyglucose (FDG) PET/CT confirmed nearly concordant high C-X-C motif chemokine receptor 4 (CXCR4) expression and high glucose metabolism, respectively, in multiple lesions in a patient with multiple myeloma and significantly lower FDG uptake after ⁹⁰Y-pentixather in all lesions, indicating excellent therapeutic response. B, Scintigraphic images in a patient at serial time points after ¹⁷⁷Lu-pentixather confirmed CXCR4 specificity and binding. (Reprinted, with permission, from reference .)