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Pharmaceuticals
Special Issues
Preparation of Radiopharmaceuticals and Their Use in Drug Development
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Preparation of Radiopharmaceuticals and Their Use in Drug Development

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (30 May 2015) | Viewed by 25946

Special Issue Editor

Dr. Svend Borup Jensen

E-Mail Website
Guest Editor
Nuklearmedicinsk Afdeling—Hobrovej 18-22, Postboks 365, 9100 Aalborg, Denmark
Interests: radiochemistry; radiopharmacy; GMP-production; drug degradation; receptor kinetics; analytical methods; chelation; medicinal chemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The journals Molecules and Pharmaceuticals will jointly be publishing a Special Issue covering the topic "Preparation of Radiopharmaceuticals and Their Use in Drug Development". I would like to invite you to make submissions addressing topics regarding Preparation of Radiopharmaceuticals with the aim at exploring their potential use in Drug Discovery.

The use of radiopharmaceuticals in drug development has many different applications.

Labeling a potential drug with a radionuclide for imaging and inject radiopharmaceuticals into animals or human can immediately give information about the in vivo destiny of the compound by applying PET- or SPECT scanners Does a radioactive drug accumulation in the site where the drug is supposed to have its effect or does it not reach the target organ or tumor at all? If radionuclides are employed throughout the whole process of developing new drugs, especially if the results are negative and the potential drug can be discarded early on in the process, a lot of effort and money can be saved. An alternative way of obtaining information about the in vivo destiny/effect of a potential drug is to imagine, for example, a target organ or a tumor with radiopharmaceuticals before and after treatment with a drug. This technique will most likely be widespread when it comes to personalized medicine, when a scan with a radiopharmaceutical can determine if a certain drug has its desired effect or if the physician has to try something else.

Determining how a drug is metabolized is an integrated part of drug development. Labeling a drug with radionuclide giving it a radioactive tag can help to find it subsequently and to quantify metabolites. If the metabolites can be extracted, the solutions can be examined by common analytical measurements. If the metabolites are incorporated into tissue and for that reason more difficult to find, a quick radioactive measurement can determine which tissue samples contain metabolites and/or radioactive labeled drug.

Using ionizing radiation in the treatment of tumor is also an application for radiopharmaceuticals which is expected to expand greatly in the years to come. By labeling a specific compounds with a radionuclide used for diagnostics we can see if it accumulates in the tumor. The same compound is thereafter combined with a radionuclide for treatment.

The purpose of this Special Issue is to host research and review papers on the Preparation of Radiopharmaceuticals and their potential use in Drug Discovery.

Dr. Svend Borup Jensen
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.


Keywords

  • radioactive isotopes
  • PET and SPEC molecules
  • radiopharmaceuticals
  • quality control
  • Purification techniques
  • ionizing radiation

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Published Papers (3 papers)

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Research

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3124 KiB  
Article
Bench to Bedside: Stability Studies of GMP Produced Trastuzumab-TCMC in Support of a Clinical Trial
by Diane E. Milenic, Kwamena E. Baidoo and Martin W. Brechbiel
Pharmaceuticals 2015, 8(3), 435-454; https://doi.org/10.3390/ph8030435 - 29 Jul 2015
Cited by 12 | Viewed by 7963
Abstract
The first-in-human phase 1 clinical radioimmunotherapy (RIT) trial with 212Pb-1,4,7,10-tetraaza-1,4,7,10-tetra-(2-carbamoylmethyl)-cyclododecane-trastuzumab (212Pb-TCMC-trastuzumab) was completed in October 2014 as a joint effort at the University of Alabama (UAB) and the University of California San Diego Moores Cancer Center. The preliminary reports indicate [...] Read more.
The first-in-human phase 1 clinical radioimmunotherapy (RIT) trial with 212Pb-1,4,7,10-tetraaza-1,4,7,10-tetra-(2-carbamoylmethyl)-cyclododecane-trastuzumab (212Pb-TCMC-trastuzumab) was completed in October 2014 as a joint effort at the University of Alabama (UAB) and the University of California San Diego Moores Cancer Center. The preliminary reports indicate that after five dose-levels of intraperitoneally administered 212Pb-TCMC-trastuzumab, patients with carcinomatosis experienced minimal agent-related toxicity. This report presents the data accumulated to date on the stability of the clinical grade, produced according to current good manufacturing practices (cGMP), TCMC-trastuzumab conducted in support of that clinical trial. Of the eleven tests performed with the cGMP TCMC-trastuzumab all but one remained within specifications throughout the 5 year testing period. The protein concentration varied by 0.01 mg/mL at 48 months. Two other assays, ion-exchange high performance liquid chromatography (IEX-HPLC) and a competitive radioimmunoassay (RIA) indicated that the cGMP TCMC-trastuzumab integrity may be changing, although the change thus far is within specifications. Subsequent stability testing will confirm if a trend has truly developed. The cGMP TCMC-trastuzumab was also evaluated for tolerance to higher temperatures and the potential of storage at −80 °C. The immunoconjugate proved stable when subjected to the lower temperatures and to multiple freeze-thaw cycles. The size exclusion (SE) HPLC analysis of the 203Pb-TCMC-trastuzumab was the only indicator that cGMP TCMC-trastuzumab may be sensitive to storage at 37 °C for 3 months. Full article
(This article belongs to the Special Issue Preparation of Radiopharmaceuticals and Their Use in Drug Development)
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2811 KiB  
Article
Toxicological Studies of 212Pb Intravenously or Intraperitoneally Injected into Mice for a Phase 1 Trial
by Diane E. Milenic, Alfredo A. Molinolo, María S. Solivella, Eileen Banaga, Julien Torgue, Sarah Besnainou, Martin W. Brechbiel and Kwamena E. Baidoo
Pharmaceuticals 2015, 8(3), 416-434; https://doi.org/10.3390/ph8030416 - 24 Jul 2015
Cited by 16 | Viewed by 5996
Abstract
Faced with the novelty of a 212Pb-labeled monoclonal antibody (mAb) for clinical translation, concerns were expressed by the Food and Drug Administration (FDA) regarding 212Pb prematurely released from the mAb-chelate conjugate. The objective of this study was to simulate the worst [...] Read more.
Faced with the novelty of a 212Pb-labeled monoclonal antibody (mAb) for clinical translation, concerns were expressed by the Food and Drug Administration (FDA) regarding 212Pb prematurely released from the mAb-chelate conjugate. The objective of this study was to simulate the worst case scenario of such a failure. Groups of Balb/c mice (n = 9–20) were administered 212Pb by intraperitoneal (0.0925–1.85 MBq) or intravenous (0.0925–1.11 MBq) injection and then euthanized at 7 or 90 days to assess acute or chronic effects. Weights were recorded prior to injection of the 212Pb and at the end of the observation periods. Blood samples were collected for clinical chemistry and blood cell analysis. Thirty tissues were harvested and formalin fixed for histopathological examination. Treatment related effects of the 212Pb were observed in the bone marrow, spleen, kidneys and the liver. Histological alterations in these organs were considered mild to moderate, indicating low grade toxicity, and not considered severe enough to affect function. This data was presented to the FDA and determined to be acceptable. The clinical trial with 212Pb-TCMC-trastuzumab was approved in January 2011 and the trial opened at the University of Alabama at Birmingham (UAB) in July. Full article
(This article belongs to the Special Issue Preparation of Radiopharmaceuticals and Their Use in Drug Development)
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Review

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794 KiB  
Review
A Critical Review of Alpha Radionuclide Therapy—How to Deal with Recoiling Daughters?
by Robin M. De Kruijff, Hubert T. Wolterbeek and Antonia G. Denkova
Pharmaceuticals 2015, 8(2), 321-336; https://doi.org/10.3390/ph8020321 - 10 Jun 2015
Cited by 157 | Viewed by 11249
Abstract
This review presents an overview of the successes and challenges currently faced in alpha radionuclide therapy. Alpha particles have an advantage in killing tumour cells as compared to beta or gamma radiation due to their short penetration depth and high linear energy transfer [...] Read more.
This review presents an overview of the successes and challenges currently faced in alpha radionuclide therapy. Alpha particles have an advantage in killing tumour cells as compared to beta or gamma radiation due to their short penetration depth and high linear energy transfer (LET). Touching briefly on the clinical successes of radionuclides emitting only one alpha particle, the main focus of this article lies on those alpha-emitting radionuclides with multiple alpha-emitting daughters in their decay chain. While having the advantage of longer half-lives, the recoiled daughters of radionuclides like 224Ra (radium), 223Ra, and 225Ac (actinium) can do significant damage to healthy tissue when not retained at the tumour site. Three different approaches to deal with this problem are discussed: encapsulation in a nano-carrier, fast uptake of the alpha emitting radionuclides in tumour cells, and local administration. Each approach has been shown to have its advantages and disadvantages, but when larger activities need to be used clinically, nano-carriers appear to be the most promising solution for reducing toxic effects, provided there is no accumulation in healthy tissue. Full article
(This article belongs to the Special Issue Preparation of Radiopharmaceuticals and Their Use in Drug Development)
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