Evidence map›Paper›PMID 38641714›Full record

ArticleEuropean journal of nuclear medicine and molecular imaging2024

Combined, yet separate: cocktails of carriers (not drugs) for actinium-225 α-particle therapy of solid tumors expressing moderate-to-low levels of targetable markers.

Rajiv Ranjit Nair, Aprameya Prasad, Omkar Bhatavdekar, Aira Sarkar, Kathleen L Gabrielson, Stavroula Sofou

Abstract read
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In one paragraph

Article in European journal of nuclear medicine and molecular imaging, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
2.8field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 7 citations in OpenAlex.

  1. Dual-tracer PET/CT and cocktail therapy with [European journal of nuclear medicine and molecular imaging · 2026
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Rajiv Ranjit Nair *Chemical and Biomolecular Engineering (ChemBE), Institute for NanoBioTechnology (INBT), Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218, USA.
Aprameya Prasad *Chemical and Biomolecular Engineering (ChemBE), Institute for NanoBioTechnology (INBT), Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218, USA.
Omkar BhatavdekarChemical and Biomolecular Engineering (ChemBE), Institute for NanoBioTechnology (INBT), Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218, USA.
Aira SarkarChemical and Biomolecular Engineering (ChemBE), Institute for NanoBioTechnology (INBT), Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218, USA.
Kathleen L GabrielsonMolecular and Comparative Pathobiology, Johns Hopkins University, Baltimore, MD, USA.
Stavroula SofouChemical and Biomolecular Engineering (ChemBE), Institute for NanoBioTechnology (INBT), Johns Hopkins University, 3400 North Charles Street, Baltimore, MD, 21218, USA. ssofou1@jhu.edu.ORCID 0000-0003-1735-326X
Johns Hopkins University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Alpha-particle radionuclide-antibody conjugates are being clinically evaluated against solid tumors even when they moderately express the targeted markers. At this limit of lower tumor-absorbed doses, to maintain efficacy, the few(er) intratumorally delivered alpha-particles need to traverse/hit as many different cancer cells as possible. We complement antibody-radioconjugate therapies with a separate nanocarrier delivering a fraction of the same total injected radioactivity to tumor regions geographically different than those affected by targeting antibodies; these carrier-cocktails collectively distribute the alpha-particle emitters better.

methodsThe efficacy of actinium-225 delivered by our carrier-cocktails was assessed in vitro and on mice with orthotopic MDA-MB-436 and/or MDA-MB-231 triple-negative breast cancers and/or an ectopic BxPC3 pancreatic cancer. Cells/tumors were chosen to express low-to-moderate levels of HER1, as model antibody-targeted marker.

resultsIndependent of cell line, antibody-radioconjugates were most lethal on cell monolayers. On spheroids, with radii greater than alpha-particles' range, carrier-cocktails improved killing efficacy (p < 0.0500). Treatment with carrier-cocktails decreased the MDA-MB-436 and MDA-MB-231 orthotopic tumor volumes by 73.7% and 72.1%, respectively, relative to treatment with antibody-radioconjugates alone, at same total injected radioactivity; these carrier-cocktails completely eliminated formation of spontaneous metastases vs. 50% and 25% elimination in mice treated with antibody-radioconjugates alone. In BxPC3 tumor-bearing mice, carrier-cocktails increased the median survival to 25-26 days (in male-female animals) vs. 20-21 days of mice treated with antibody-radioconjugates alone (vs. 17 days for non-treated animals). Survival with carrier-cocktail radiotherapy was further prolonged by pre-injecting low-dose, standard-of-care, gemcitabine (p = 0.0390).

conclusionTumor-agnostic carrier-cocktails significantly enhance the therapeutic efficacy of existing alpha-particle radionuclide-antibody treatments.

Indexed as

ActiniumAlpha ParticlesAnimalsBiomarkers, TumorCell Line, TumorDrug CarriersFemaleHumansImmunoconjugatesMiceActiniumActinium-225Biomarkers, TumorDrug CarriersImmunoconjugatesActinium-225Alpha-particle radiotherapyAntibody-targeted radiotherapyIntratumor distributionsLow targeted markersSpheroids

Identifiers

PMID38641714
OpenAlexW4394978280

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.