Abstract
The in vivo-generator radionuclides 140Nd (t1/2 = 3.4 d) and 134Ce (t1/2 = 3.2 d) were used to trace a urokinase-type plasminogen activator (uPA)-targeting mouse monoclonal antibody, ATN-291, in U87 MG xenograft tumor-bearing mice. ATN-291 is known to internalize on the uPA/uPA-receptor pair, making it an appropriate targeting vector for investigating the fate of in vivo generator daughters on internalizing probes. Ante-mortem and post-mortem PET imaging at 120 h post-injection gave no indication of redistribution of the positron emitting daughter nuclides 134La and 140Pr from tumor tissue (p > 0.5). The lack of redistribution indicates that the parent radionuclides 134Ce and 140Nd could be considered as long-lived PET-diagnostic matches to therapeutic radionuclides like 177Lu, 161Tb and 225Ac when internalizing bioconjugates are employed.
Highlights
The in vivo-generator radionuclides 140Nd (t1/2 = 3.4 d) and 134Ce (t1/2 = 3.2 d) were used to trace a urokinase-type plasminogen activator-targeting mouse monoclonal antibody, ATN-291, in U87 MG xenograft tumor-bearing mice
The present study is a test-case for performing imaging and biodistribution studies with in vivo generators bound to an internalizing probe, the mouse monoclonal antibody ATN-291
It is important to note that signals from the “heart” Regions of interest (ROIs) include the blood pool in the PET images but only the myocardium was used in the ex vivo biodistribution
Summary
The in vivo-generator radionuclides 140Nd (t1/2 = 3.4 d) and 134Ce (t1/2 = 3.2 d) were used to trace a urokinase-type plasminogen activator (uPA)-targeting mouse monoclonal antibody, ATN-291, in U87 MG xenograft tumor-bearing mice. The radionuclides cerium-134 (134Ce, t1/2 = 3.2 d, EC) and neodymium-140 (140Nd, t1/2 = 3.4 d, EC) provide an interesting opportunity to study the in vivo behavior of long-lived and decay-released r adionuclides[3,4] Both of these long-lived radiolanthanides decay to relatively short-lived positron emitting daughters: lanthanum-134 (t1/2 = 6.5 min, 64% β+) and praseodymium-140 (140Pr, t1/2 = 3.4 min, 51% β+) respectively (see Fig. 1). Due to the delayed positron emission, 140Nd and 134Ce, are deemed PET “in vivo generators”[5] For both of these decay chains, the parent EC decay is locally disruptive and results in a separation of the daughter radionuclide from tracer-radioconjugates with roughly 100% efficiency (see, e.g.6 and discussion in[5]). This implies that a payload-based therapy with ATN-291
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