Important Clinical Applications of 188Rhenium for Radionuclide Therapy

Abstract

Although established clinical utility is of key importance in choosing agents for radionuclide therapy, other key factors include costs and GMP availability of sterile, pyrogen-free, regulatory approved radiopharmaceuticals. No-carrieradded (NCA) 188 Rhenium(188 Re, 16.9 hour half-life; 155 keV gamma emission) is available on demand as 188 Reperrhenate from saline elution of a 188 Tungsten/ 188 Rhenium(188 W/ 188 Re) generator. The availability and superb radionuclidic and chemical properties make 188 Re an excellent candidate for radionuclide therapy. This radioisotope is readily attached to a variety of targeting agents and also emits high energy beta particles (Emax 2.12 MeV) for therapy. Over the last 30 years the effectiveness of 188 Re for a variety of therapeutic applications has been established in multiple clinical studies. This overview provides a brief summary of clinical applications with 188 Re-labeled agents as an introduction to the detailed clinical discussions in the following papers. Although 188 Re-labeled radiopharmaceuticals for routine clinical use and accompanying reimbursement are not yet commercially available, several agents have been evaluated in clinical studies. In addition, a large number of 188 Re radiopharmaceutical agents have been developed and evaluated in pre-clinical studies over the last three decades. This review focuses on providing examples of 188 Re-labeled radiopharmaceutical agents which have entered late stage clinical use and have demonstrated good efficacy. These key applications include palliative treatment of skeletal metastases, intra-arterial therapy of liver cancer and post PTCA intravascular inhibition of arterial restenosis. Also, 188 Re radiopharmaceuticals had been developed and initially assessed for synovectomy and for marrow suppression. More recently, a unique device-based technology has entered clinical use for therapy of non-melanoma skin cancer using a 188 Re topical cream. Finally, 188 Re-antibodies are being developed for the potential therapy of infectious disease and this unique new therapeutic strategy is expected to enter clinical trials in the near future.

Fundamentals of Rhenium-188 Radiopharmaceutical Chemistry

“…A reproducible procedure for the high-yield preparation of 188 Re radiopharmaceuticals from generator-produced [ 188 Re][ReO 4 ] − has been successfully achieved only with a few cores. Specifically, 188 Re-radiopharmaceuticals bearing the Re(V) oxo and Re(V) nitrido cores have been produced almost exclusively at tracer level and evaluated in human studies [ 4 , 27 ]. Exceptions are the 188 Re radiopharmaceuticals [ 188 Re][Re(PhCS 3 ) 2 (PhCS 2 )] (Ph = phenyl group), which has been introduced for the treatment of liver cancer [ 3 , 28 ] and incorporates the [Re III (S 2 )(S 3 ) 2 ] functional moiety, and the polymeric 188 Re bisphosphonate agents of unknown structure used for bone-pain palliation [ 29 , 30 ].…”

“…Current applications of 188 Re in the clinic have been reviewed extensively in other articles [ 1 , 3 , 4 , 25 , 26 , 27 ]. This review aims to discuss a more basic approach for a rational design of 188 Re radiopharmaceuticals by considering both nuclear and electronic properties of rhenium complexes.…”

“…As mentioned previously, only a small number of 188 Re radiopharmaceuticals have been successfully introduced into the clinical use using freeze-dried kit formulations. The design of these radiopharmaceuticals was almost invariably based on the chemistry of Re(V) oxo and Re(V) nitrido cores and of 188 Re complexes containing the sulphur rich Re III (S 3 ) 2 (S 2 ) metallic group [ 3 , 4 , 18 , 25 , 27 , 28 ].…”

Bifunctional chelators for radiorhenium: past, present and future outlook

“…Over the past decade, many interesting and comprehensive reviews on the different types of BFCs for radiorhenium in the context of TRNT have been written. 13,18,[22][23][24][25] In fact, in 2017 an entire special issue by the International Journal of Nuclear Medicine and Research was dedicated to the use of 188 Re in radionuclide therapy. 26 The purpose of this review is to provide a brief summary of some of the most notable chelators, as well as give an up-to-date…”