WO2023059111A1 - Composé de gadolinium et composition pharmaceutique pour le diagnostic et le traitement du cancer de la prostate le comprenant - Google Patents

Composé de gadolinium et composition pharmaceutique pour le diagnostic et le traitement du cancer de la prostate le comprenant Download PDF

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Publication number
WO2023059111A1
WO2023059111A1 PCT/KR2022/015062 KR2022015062W WO2023059111A1 WO 2023059111 A1 WO2023059111 A1 WO 2023059111A1 KR 2022015062 W KR2022015062 W KR 2022015062W WO 2023059111 A1 WO2023059111 A1 WO 2023059111A1
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Prior art keywords
compound
prostate cancer
pharmaceutically acceptable
racemate
stereoisomer
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PCT/KR2022/015062
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English (en)
Inventor
Dae Yoon Chi
Hee Seup Kil
Min Hwan Kim
Kyo Chul Lee
Yong Jin Lee
Ji Ae Park
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Futurechem Co., Ltd.
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Publication of WO2023059111A1 publication Critical patent/WO2023059111A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/009—Neutron capture therapy, e.g. using uranium or non-boron material
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic System
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/542—Carboxylic acids, e.g. a fatty acid or an amino acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
    • A61K49/085—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier conjugated systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
    • A61K49/10—Organic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
    • A61K49/10—Organic compounds
    • A61K49/101—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals
    • A61K49/106—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being cyclic, e.g. DOTA
    • A61K49/108—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being cyclic, e.g. DOTA the metal complex being Gd-DOTA

Definitions

  • the present invention relates to a gadolinium compound in which a prostate-specific membrane antigen (hereinafter also referred to as "PSMA") target substance is introduced, and a pharmaceutical composition comprising the gadolinium compound for diagnosing and/or treating prostate cancer.
  • PSMA prostate-specific membrane antigen
  • Prostate cancer is the most common male cancer in Western countries and the fourth highest incidence in Korea, and recently, the number of patients has been rapidly increasing. Prostate cancer is highly malignant and frequently metastasizes to other organs.
  • prostate cancer is suspected from a blood test, rectal examination, ultrasonography and the like, it is definitively diagnosed by a tissue biopsy.
  • ultrasonography has been conducted with reference to a prostate magnetic resonance imaging (hereinafter also referred to as MRI) taken prior to the tissue biopsy, and a method of performing a tissue biopsy on lesions suspected as prostate cancer has also been conducted.
  • MRI-based prostate-targeted tissue biopsy shows higher diagnostic accuracy compared to the conventional tissue biopsy.
  • MRI is an essential examination method not only for diagnosing prostate cancer, but also for determining stage of disease to decide treatment guidelines, and evaluating post-treatment therapeutic effects and likelihood of recurrence.
  • MRI is a method for acquiring anatomical, physiological and biochemical information on the body as images with a phenomenon in which the spins of hydrogen atoms are relaxed in a magnetic field, and has an advantage of being non-invasive real-time imaging, and thus is useful for diagnosing diseases.
  • An MRI contrast agent may further increase the contrast of tissue by altering the magnetic relaxation time of water molecules in the tissue.
  • a typical MRI contrast agent currently used in clinical practice is Gd-DTPA or Gd-DOTA in which gadolinium metal is chelated with a ligand such as diethylenetriamine pentaacetic acid (DTPA) or 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA).
  • DTPA diethylenetriamine pentaacetic acid
  • DOTA 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid
  • Gd-DTPA and Gd-DOTA have no specificity for cancer cells, and their imaging effects on cancer cells do not last long, which make them inefficient for cancer diagnosis.
  • an MRI contrast agent in which a substance specific for cancer cells is introduced into a ligand have been developed (Angew. Chem. Int. Ed., 2015, 54, 10778-10782).
  • Prostate-specific membrane antigen is a protein to be overexpressed on the surface of most prostate cancer cells. Recently, research has been actively conducted on a compound targeting PSMA and a radiopharmaceutical in which a radioisotope is labeled on the compound (KR10-2021-0046909A).
  • a Neutron Capture Therapy is a next-generation cancer treatment technology that minimizes damage to normal cells and selectively kills cancer cells only, and has been introduced to solve the side effects of anti-cancer treatment that damages not only cancer cells but also normal cells.
  • the principle of the treatment is that when after injecting a neutron-absorbing substance into cancer cells, neutrons are irradiated, high-energy gamma rays and auger electrons are emitted from the cancer cells where the neutron-absorbing substance has been accumulated, and radiation and electron beams emitted therefrom kill the cancer cells.
  • Gadolinium (Gd) and boron (B) are typical atoms that emit radiation for treating tumors by capturing neutrons.
  • Gadolinium-based gadolinium neutron capture therapy (Gd-NCT) agents have recently attracted attention as a new research field because of their physical properties providing a contrast effect in magnetic resonance imaging.
  • Gadolinium is the element that absorbs neutrons best due to its wide neutron absorption cross-section, and has the largest number of electrons not paired in atoms and ions. Boron kills cancer cells with alpha particles which are helium nuclei generated when irradiating neutrons, whereas gadolinium kills cancer cells with high-energy gamma rays and electrons generated when absorbing neutrons.
  • gadolinium neutron capture therapy (Gd-NCT) is in an early stage globally.
  • an existing MRI contrast agent such as Gd-DTPA or Gd-DOTA
  • these existing radiopharmaceuticals are disadvantageous in that their ability to target cancer cells is low and their therapeutic effects are low (Future Med. Chem., 2016, 8, 899-917).
  • An object of the present invention is to provide a novel gadolinium compound that exhibits a diagnostic or therapeutic effect for prostate cancer.
  • Another object of the present invention is to provide a pharmaceutical composition for diagnosing prostate cancer, comprising the gadolinium compound, or a stereoisomer, a racemate, a hydrate or a pharmaceutically acceptable salt thereof.
  • Still another object of the present invention is to provide a pharmaceutical composition for treating prostate cancer, comprising the gadolinium compound, or a stereoisomer, a racemate, a hydrate or a pharmaceutically acceptable salt thereof.
  • Yet another object of the present invention is to provide a composition for diagnosing and treating prostate cancer, comprising the gadolinium compound, or a stereoisomer, a racemate, a hydrate or a pharmaceutically acceptable salt thereof, and which can provide an effect of diagnosing and treating prostate cancer simultaneously.
  • the present inventors have solved the above-described technical problems by demonstrating that it is possible to be used for diagnosing and treating prostate cancer when a PSMA target compound with a high binding affinity to prostate cancer is combined with gadolinium.
  • R is hydrogen, a C 1-6 alkyl or a halogen atom
  • L is (CH 2 ) n , wherein n is an integer any of 0 to 3.
  • a pharmaceutical composition for diagnosing prostate cancer comprising the compound of Formula 1, or a stereoisomer, a racemate, a hydrate or pharmaceutically acceptable salt thereof.
  • a pharmaceutical composition for treating prostate cancer comprising the compound of Formula 1, or a stereoisomer, a racemate, a hydrate or pharmaceutically acceptable salt thereof.
  • a pharmaceutical composition for diagnosing and treating prostate cancer comprising the compound of Formula 1, or a stereoisomer, a racemate, a hydrate or pharmaceutically acceptable salt thereof, and providing the effect of diagnosing and treating prostate cancer simultaneously.
  • a gadolinium compound which can be used for diagnosing and/or treating prostate cancer with excellent selectivity for prostate cancer and low toxicity
  • a pharmaceutical composition for diagnosing and treating prostate cancer comprising the compound, or a stereoisomer, a racemate, a hydrate of a pharmaceutically acceptable salt thereof.
  • the compound of the present invention is expected to be used as a safe and effective MRI contrast agent because a ligand having an excellent selectivity for prostate cancer is introduced into gadolinium and its cytotoxicity is low, and also to be developed as a pharmaceutical for treating prostate cancer and as a pharmaceutical providing the effect of diagnosing and treating prostate cancer simultaneously because it can provide the effect of treating prostate cancer through gadolinium neutron capture therapy.
  • Fig. 1 shows the HPLC analysis results for compound Gd-FC705 prepared in Example 1 of the present invention
  • Fig. 2 shows the results of measuring cell viability over the concentration of the compound Gd-FC705 of the present invention
  • Fig. 3 is a graph comparing the ability of the compound Gd-FC705 of the present invention to target PSMA in PSMA (+) cells and PSMA (-) cells;
  • Fig. 4A is an MRI image obtained from a mouse in which after transplanting prostate cancer, the compound Gd-FC705 of the present invention was injected;
  • Fig. 4B is a graph comparing the signal from PSMA (+) tumor site with the signal from PSMA (-) tumor site in MRI image obtained after injecting the compound Gd-FC705 of the present invention.
  • Fig. 4C is a graph comparing the signal from the compound Gd-FC705 of the present invention with the signal from Gd-DOTA in the PSMA (+) tumor MRI image.
  • An aspect of the present invention relates to a compound represented by the following Formula 1, or a stereoisomer, a racemate, a hydrate or pharmaceutically acceptable salt thereof:
  • R is hydrogen, a C 1-6 alkyl or a halogen atom
  • L is (CH 2 ) n , wherein n is an integer any of 0 to 3.
  • the C 1-6 alkyl is a linear or branched alkyl having 1 to 6 carbon atoms, and the halogen atom is selected from the group consisting of F, Cl, Br and I.
  • R may be an iodine atom (I).
  • n may be 1, 2 or 3.
  • the compound of Formula 1 may be a compound having the structure of the following Formula 2, or a stereoisomer or a racemate thereof:
  • Another aspect of the present invention relates to a pharmaceutical composition for diagnosing prostate cancer, comprising the compound of Formula 1, or a stereoisomer, a racemate, a hydrate or pharmaceutically acceptable salt thereof.
  • Still another aspect of the present invention may be a contrast agent for performing magnetic resonance imaging (MRI), comprising the pharmaceutical composition for diagnosing prostate cancer, that is, an MRI contrast agent.
  • MRI magnetic resonance imaging
  • Yet another aspect of the present invention relates to a pharmaceutical composition for treating prostate cancer, comprising the compound of Formula 1, or a stereoisomer, a racemate, a hydrate or pharmaceutically acceptable salt thereof.
  • the pharmaceutical composition for treating prostate cancer according to the present invention may be a pharmaceutical composition for treating prostate cancer, which treats prostate cancer using the ability of gadolinium to capture neutrons.
  • the compound of Formula 1 in which a ligand with excellent selectivity for prostate cancer is introduced into gadolinium can be used as a safe and effective MRI contrast agent for diagnosing prostate cancer due to its excellent ability to target prostate cancer and low cytotoxicity, and can also provide the effect of treating prostate cancer with the ability of gadolinium to capture neutrons, and therefore can provide diagnosing and treating effects simultaneously for prostate cancer.
  • yet another aspect of the present invention relates to a pharmaceutical composition simultaneously providing diagnosis and treatment of prostate cancer, comprising the compound of Formula 1, or a stereoisomer, a racemate, a hydrate or pharmaceutically acceptable salt thereof.
  • the compound of Formula 1 may be used in the form of a stereoisomer, a racemate, a hydrate or a pharmaceutically acceptable salt.
  • the pharmaceutically acceptable salt may include an alkaline metal salt or an amine salt, more specifically, a sodium salt, a meglumine salt or the like, but are not limited thereto, and any salts which have been known and typically used in the art can be used.
  • the pharmaceutical composition for diagnosing and/or treating prostate cancer may be formulated for an injection.
  • the pharmaceutical composition may comprise as a diluent a non-toxic buffer solution which is isotonic with blood, such as a phosphate buffer solution with a pH of 7.4, and the like.
  • the injection may further comprise a diluent, an excipient, an additive and the like.
  • the diluent, excipient and additive that can be used in the present invention have been widely known to a person of ordinary skill in the art, for example, through Dr. H.P. Fiedler's "Lexikon der Hilfsstoffe fur Pharmazie, Kosmetik und angrenzende füre" Encyclopaedia of auxiliaries for pharmacy, cosmetics and related fields, and the like.
  • Gadolinium(III) chloride hexahydrate (GdCl 3 .6H 2 O, 34 mg, 0.0092 mmol) dissolved in water (2 mL) was added to a solution of Compound 2 (100 mg, 0.0076 mmol) dissolved in water (2 mL), to which 1N sodium hydroxide solution was added so as to adjust pH between 7 and 8, and then the resulting mixture was stirred at room temperature for 2 hours.
  • the reaction solution was filtered, purified using high-performance liquid chromatography (HPLC) and lyophilized to obtain Compound 1 (60 mg, 54%) in a white solid.
  • HPLC conditions column, Grace (10 ⁇ m, 250 mm ⁇ 22 mm); mobile phase, 30% acetonitrile/water (0.1% trifluoroacetic acid); flow rate, 10 mL/min; UV, 220 nm; retention time, 15.3 min.
  • Fig. 1 shows HPLC analysis results of the compound Gd-FC705 prepared in Example 1.
  • the cell viability in Gd-FC705 prepared in Example 1 was measured in PSMA (+) cells and PSMA (-) cells.
  • PSMA (+) and PSMA (-) cells were maintained in RPMI1640 supplemented with 10% FBS and 1% antibiotics. The medium was replaced every 2 days, and each cell was introduced into a 96-well plate (1 ⁇ 10 4 cells/well/100 ⁇ L).
  • Gd-FC705 was added to each well at a different concentration (0 to 200 ⁇ M). After the wells were incubated at 37°C in a 5% CO 2 atmosphere for 24 hours, cell viability was measured. The results are provided in Fig. 2.
  • Gd-FC705 had no cytotoxicity at a range of 0 to 200 ⁇ M in PSMA (+) and PSMA (-) cells.
  • the magnetic relaxivity of a compound Gd-FC705 prepared in Example 1 was measured. Relaxation time was measured with a 3T (128 MHz) MRI device. An inversion-recovery pulse sequence was used to measure T1 relaxation time, and a Carr-Purcell-Meiboon-Gill (CPMG) pulse sequence was used for T2 relaxation time. Relaxivities ( r 1 , r 2 ) were calculated as inverses of relaxation times per mM (mM -1 s -1 ). Gd-DOTA (Dotarem ® ) was used as a control. The results are shown in Table 1 below.
  • Gd-FC705 is an MRI contrast agent which can effectively show signals in view that its the magnetic relaxivity is higher than that of Gd-DOTA.
  • Gd-FC705 prepared in Example 1 to target PSMA
  • cell accumulation value cell uptake
  • PSMA (+) cells cells where prostate cancer was expressed
  • PSMA (-) cells cells where prostate cancer was not expressed
  • Gd-FC705 (0.2 mM) was respectively added to PSMA (+) and PSMA (-) cells (1 ⁇ 10 4 ) and then cultured in serum-free medium for 1, 2 and 24 hours. At each time, centrifugation was performed to remove the medium and residue was washed three times with cold PBS, and then gadolinium concentration was identified with ICP-MS.
  • Fig. 3 is a graph comparing the ability of Gd-FC705 to target PSMA in PSMA (+) cells and PSMA (-) cells. According to the results in Fig. 3, the amount of Gd-FC705 bound to PSMA (+) cells was larger than the amount of Gd-FC705 bound to PSMA (-) cells, which means that Gd-FC705 has a good ability to target PSMA (+) cells.
  • An MRI image was acquired by administering Gd-FC705 prepared in Example 1 to a prostate cancer model mouse.
  • the MRI image was taken by a T1-weighted imaging method on a 3T magnetic resonance imaging system (Magnetom TrioTim, Siemens, Erlangen, Germany).
  • 0.1 mmol/kg Gd-FC705 was injected via the tail vein of an anesthetized mouse.
  • MRI images were taken before and after injection, and the results were provided in Figs. 4A to 4C.
  • MRI images acquired after injection of Gd-FC705 showed increased signal (brighter color) at PSMA (+) tumor sites, with the highest signal appearing about 1 hour after injection (Fig. 4A) and the signal appeared in PSMA (+) cells being twice or more of that in PSMA (-) cells (Fig. 4B).
  • Fig. 4C shows that in PSMA (+) cells, the signal of Gd-FC705 is higher and lasts longer than that of Gd-DOTA.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
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  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medicinal Chemistry (AREA)
  • Radiology & Medical Imaging (AREA)
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  • Engineering & Computer Science (AREA)
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  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

La présente invention concerne un composé de gadolinium ou un stéréoisomère, un racémate, un hydrate ou un sel pharmaceutiquement acceptable de celui-ci, qui peut être utilisé pour diagnostiquer et/ou traiter le cancer de la prostate avec une excellente sélectivité pour le cancer de la prostate et une faible toxicité et une composition pharmaceutique pour le diagnostic et le traitement du cancer de la prostate, comprenant un composé de gadolinium ou un stéréoisomère, un racémate, un hydrate ou un sel pharmaceutiquement acceptable de celui-ci. Le composé selon la présente invention est supposé être développé en tant qu'agent de contraste d'IRM sûr et efficace pour diagnostiquer un cancer de la prostate et un produit pharmaceutique pour son traitement, un ligand présentant une excellente sélectivité pour le cancer de la prostate étant introduit dans le gadolinium et sa toxicité est faible.
PCT/KR2022/015062 2021-10-07 2022-10-06 Composé de gadolinium et composition pharmaceutique pour le diagnostic et le traitement du cancer de la prostate le comprenant WO2023059111A1 (fr)

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KR10-2021-0133543 2021-10-07
KR1020210133543A KR20230050552A (ko) 2021-10-07 2021-10-07 가돌리늄 화합물 및 이를 포함하는 전립선암의 진단 및 치료용 약학적 조성물

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20150143995A (ko) * 2014-06-16 2015-12-24 한국원자력연구원 전립선암의 진단 및 치료를 위한 가스트린유리펩티드수용체 길항서열 기반의 신규한 봄베신 유도체 화합물
US20170128572A1 (en) * 2015-11-06 2017-05-11 Wisconsin Alumni Research Foundation Long-lived gadolinium based tumor targeted imaging and therapy agents
WO2017165473A1 (fr) * 2016-03-22 2017-09-28 The Johns Hopkins University Agents à affinité élevée ayant pour cible un antigène membranaire spécifique de la prostate, utilisés pour l'endoradiothérapie du cancer de la prostate
US20190184040A1 (en) * 2017-12-15 2019-06-20 Wisconsin Alumni Research Foundation Targeted Macrocyclic Agents for Dual Modality PET and MRI Imaging of Cancer
US20210106701A1 (en) * 2018-03-30 2021-04-15 Samsung Electronics Co., Ltd. Psma-targeted radiopharmaceutical for diagnosing and treating prostate cancer

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102412174B1 (ko) 2019-10-18 2022-06-24 (주)퓨쳐켐 암 또는 염증질환의 진단 및 치료를 위한 사전표적 방사성의약품

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20150143995A (ko) * 2014-06-16 2015-12-24 한국원자력연구원 전립선암의 진단 및 치료를 위한 가스트린유리펩티드수용체 길항서열 기반의 신규한 봄베신 유도체 화합물
US20170128572A1 (en) * 2015-11-06 2017-05-11 Wisconsin Alumni Research Foundation Long-lived gadolinium based tumor targeted imaging and therapy agents
WO2017165473A1 (fr) * 2016-03-22 2017-09-28 The Johns Hopkins University Agents à affinité élevée ayant pour cible un antigène membranaire spécifique de la prostate, utilisés pour l'endoradiothérapie du cancer de la prostate
US20190184040A1 (en) * 2017-12-15 2019-06-20 Wisconsin Alumni Research Foundation Targeted Macrocyclic Agents for Dual Modality PET and MRI Imaging of Cancer
US20210106701A1 (en) * 2018-03-30 2021-04-15 Samsung Electronics Co., Ltd. Psma-targeted radiopharmaceutical for diagnosing and treating prostate cancer

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