PRRT neuroendocrine tumor response monitored using circulating transcript analysis: the NETest.

Purpose: Peptide receptor radionuclide therapy (PRRT) is effective for metastatic/inoperable neuroendocrine tumors (NETs). Imaging response assessment is usually efficient subsequent to treatment completion. Blood biomarkers such as PRRT Predictive Quotient (PPQ) and NETest are effective in real-time.

PRRT genomic signature in blood for prediction of Lu-octreotate efficacy.

Background: Peptide receptor radionuclide therapy (PRRT) utilizes somatostatin receptor (SSR) overexpression on neuroendocrine tumors (NET) to deliver targeted radiotherapy. Intensity of uptake at imaging is considered related to efficacy but has low sensitivity. A pretreatment strategy to determine individual PRRT response remains a key unmet need.

Long-Term Efficacy, Survival, and Safety of [Lu-DOTA,Tyr]octreotate in Patients with Gastroenteropancreatic and Bronchial Neuroendocrine Tumors.

Bronchial and gastroenteropancreatic neuroendocrine tumors (NET) are slow-growing tumors, which frequently express somatostatin receptors on their cell membranes. These receptors are targets for therapy with Lutetium-177-labeled somatostatin analogues. We have treated over 1,200 patients with peptide receptor radionuclide therapy (PRRT) with [Lu-DOTA,Tyr]octreotate (Lu-DOTATATE) since the year 2000 and present the results on efficacy, survival, and toxicity of this therapy.

Pitfalls in the response evaluation after peptide receptor radionuclide therapy with [Lu-DOTA,Tyr]octreotate.

Peptide receptor radionuclide therapy (PRRT) with [Lu-DOTA,Tyr]octreotate (Lu-DOTATATE) is a treatment with good results in patients with metastatic gastroenteropancreatic neuroendocrine tumours (GEPNETs). However, there are some pitfalls that should be taken into consideration when evaluating the treatment response after PRRT. 354 Dutch patients with GEPNETs who were treated with Lu-DOTATATE between March 2000 and December 2011 were retrospectively selected.

Nephrotoxicity after PRRT with (177)Lu-DOTA-octreotate.

Purpose: After peptide receptor radionuclide therapy (PRRT), renal toxicity may occur, particular in PRRT with (90)Y-labelled somatostatin analogues. Risk factors have been identified for increased probability of developing renal toxicity after PRRT, including hypertension, diabetes and age. We investigated the renal function over time, the incidence of nephrotoxicity and associated risk factors in patients treated with PRRT with [(177)Lu-DOTA(0),Tyr(3)]-Octreotate ((177)Lu-Octreotate).

GEPNETs update: Radionuclide therapy in neuroendocrine tumors.

Peptide receptor radionuclide therapy (PRRT) is a promising new treatment modality for inoperable or metastasized gastroenteropancreatic neuroendocrine tumors (GEPNETs) patients. Most studies report objective response rates in 15-35% of patients. Also, outcome in terms of progression free survival (PFS) and overall survival compares very favorably with that for somatostatin analogs, chemotherapy, or new, 'targeted' therapies.

NMDA receptor activation suppresses microtubule growth and spine entry.

Dynamic microtubules are important to maintain neuronal morphology and function, but whether neuronal activity affects the organization of dynamic microtubules is unknown. Here, we show that a protocol to induce NMDA-dependent long-term depression (LTD) rapidly attenuates microtubule dynamics in primary rat hippocampal neurons, removing the microtubule-binding protein EB3 from the growing microtubule plus-ends in dendrites. This effect requires the entry of calcium and is mediated by activation of NR2B-containing NMDA-type glutamate receptor.

Probing intracellular motor protein activity using an inducible cargo trafficking assay.

Although purified cytoskeletal motor proteins have been studied extensively with the use of in vitro approaches, a generic approach to selectively probe actin and microtubule-based motor protein activity inside living cells is lacking. To examine specific motor activity inside living cells, we utilized the FKBP-rapalog-FRB heterodimerization system to develop an in vivo peroxisomal trafficking assay that allows inducible recruitment of exogenous and endogenous kinesin, dynein, and myosin motors to drive specific cargo transport. We demonstrate that cargo rapidly redistributes with distinct dynamics for each respective motor, and that combined (antagonistic) actions of more complex motor combinations can also be probed.