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Tumor-Targeting Radioligands for Molecular Imaging and Therapy

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A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Radiopharmaceutical Sciences".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 18107

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Special Issue Editors

Dr. Petra Kolenc

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Guest Editor

Department of Nuclear Medicine, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
Interests: radiopharmacy; tranlational studies; peptide-based radiopharmaceuticals; molecular imaging

Dr. Rosalba Mansi

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Guest Editor

Division of Radiopharmaceutical Chemistry, Clinic of Radiology and Nuclear Medicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland
Interests: anti-tumour drug design and synthesis; nuclear imaging; targeted radionuclide therapy; preclinical development of novel peptide-based radiopharmaceuticals; radiopharmacy

Dr. Marko Krošelj

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Department of Nuclear Medicine, University Medical Centre Ljubljana, Zaloška 7, 1000 Ljubljana, Slovenia
Interests: radiopharmaceuticals; radiopharmacy; targeted radionuclide therapy; nuclear medicine; molecular imaging

Special Issue Information

Dear Colleagues,

Cancer is one of the leading causes of death worldwide. Timely diagnosis of the disease is of utmost importance to support informed decision making and to improve therapy efficacy. Radiopharmaceuticals are vital components of nuclear medicine encompassing such diagnostic methods as single-photon emission computed tomography (SPECT) or positron emission tomography (PET). The increasing development and successful clinical translation of novel radiopharmaceuticals for cancer therapy, such as [¹⁷⁷Lu]Lu-DOTATATE and [¹⁷⁷Lu]Lu-PSMA-617 paved the way for new and exciting research in the field of nuclear medicine.

Although various large molecules or nanoparticles are persistently taking their part in new radiopharmaceutical developments, the majority of radiopharmaceuticals still belong to smaller molecules – radioligands, such as radiolabeled amino acids, peptide-based molecules, peptidomimetics, small-molecule inhibitors targeting e.g. prostate-specific membrane antigen (PSMA) or fibroblast activation protein (FAP), etc. One of the most important features of the radiopharmaceuticals with low molecular weight compared to larger molecules is their favourable pharmacokinetics. With high capillary permeability, fast penetration from the blood pool to the extracellular space, distribution and binding to the specific target and at the same time rapid clearance from non-target tissues, most pertinent features of ideal radiopharmaceutical can be achieved.

This Special Issue titled “Tumor-Targeting radioligands for Molecular Imaging and Therapy” aims to provide the most recent developments and quests for novel ideal radiopharmaceutical for successful diagnosis, therapy or even theranostics of various tumors. You are kindly invited to contribute either with original article or a review.

Dr. Petra Kolenc
Dr. Rosalba Mansi
Dr. Marko Krošelj
Guest Editors

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Keywords

tumor-targeting ligands
receptor targeting
tumor microenvironment
amino acids
peptide-based radiopharmaceuticals
peptidomimetics
molecular imaging
theranostics
translational study

Published Papers (9 papers)

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Research

19 pages, 2686 KiB

Open AccessArticle

On the Road towards Small-Molecule Programmed Cell Death 1 Ligand 1 Positron Emission Tomography Tracers: A Ligand-Based Drug Design Approach

by Karsten Bamminger, Verena Pichler, Chrysoula Vraka, Tina Nehring, Katharina Pallitsch, Barbara Lieder, Marcus Hacker and Wolfgang Wadsak

Pharmaceuticals 2023, 16(7), 1051; https://doi.org/10.3390/ph16071051 - 24 Jul 2023

Cited by 3 | Viewed by 1192

Abstract

PD-1/PD-L1 immune checkpoint blockade for cancer therapy showed promising results in clinical studies. Further endeavors are required to enhance patient stratification, as, at present, only a small portion of patients with PD-L1-positive tumors (as determined by PD-L1 targeted immunohistochemistry; IHC) benefit from anti-PD-1/PD-L1 immunotherapy. This can be explained by the heterogeneity of tumor lesions and the intrinsic limitation of multiple biopsies. Consequently, non-invasive in vivo quantification of PD-L1 on tumors and metastases throughout the entire body using positron emission tomography (PET) imaging holds the potential to augment patient stratification. Within the scope of this work, six new small molecules were synthesized by following a ligand-based drug design approach supported by computational docking utilizing lead structures based on the (2-methyl-[1,1′-biphenyl]-3-yl)methanol scaffold and evaluated in vitro for potential future use as PD-L1 PET tracers. The results demonstrated binding affinities in the nanomolar to micromolar range for lead structures and newly prepared molecules, respectively. Carbon-11 labeling was successfully and selectively established and optimized with very good radiochemical conversions of up to 57%. The obtained insights into the significance of polar intermolecular interactions, along with the successful radiosyntheses, could contribute substantially to the future development of small-molecule PD-L1 PET tracers. Full article

(This article belongs to the Special Issue Tumor-Targeting Radioligands for Molecular Imaging and Therapy)

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17 pages, 1263 KiB

Open AccessArticle

Effects of Side Chain and Peptide Bond Modifications on the Targeting Properties of Stabilized Minigastrin Analogs

by Taraneh Sadat Zavvar, Anton Amadeus Hörmann, Maximilian Klingler, Dominik Summer, Christine Rangger, Laurence Desrues, Hélène Castel, Pierrick Gandolfo and Elisabeth von Guggenberg

Pharmaceuticals 2023, 16(2), 278; https://doi.org/10.3390/ph16020278 - 13 Feb 2023

Cited by 2 | Viewed by 1665

Abstract

Different attempts have been made in the past two decades to develop radiolabeled peptide conjugates with enhanced pharmacokinetic properties in order to improve the application for tumor imaging and peptide receptor radionuclide therapy (PRRT), which targets the cholecystokinin-2 receptor (CCK2R). In this paper, the influence of different side chain and peptide bond modifications has been explored for the minigastrin analog DOTA-DGlu-Ala-Tyr-Gly-Trp-(N-Me)Nle-Asp-1Nal-NH₂ (DOTA-MGS5). Based on this lead structure, five new derivatives were synthesized for radiolabeling with trivalent radiometals. Different chemical and biological properties of the new derivatives were analyzed. Receptor interaction of the peptide derivatives and cell internalization of the radiolabeled peptides were studied in A431-CCK2R cells. The stability of the radiolabeled peptides in vivo was investigated using BALB/c mice. Tumor targeting of all ¹¹¹In-labeled peptide conjugates, and of a selected compound radiolabeled with gallium-68 and lutetium-177, was evaluated in BALB/c nude mice xenografted with A431-CCK2R and A431-mock cells. All ¹¹¹In-labeled conjugates, except [¹¹¹In]In-DOTA-[Phe⁸]MGS5, showed a high resistance against enzymatic degradation. A high receptor affinity with IC₅₀ values in the low nanomolar range was confirmed for most of the peptide derivatives. The specific cell internalization over time was 35.3–47.3% for all radiopeptides 4 h after incubation. Only [¹¹¹In]In-DOTA-MGS5[NHCH₃] exhibited a lower cell internalization of 6.6 ± 2.8%. An overall improved resistance against enzymatic degradation was confirmed in vivo. Of the radiopeptides studied, [¹¹¹In]In-DOTA-[(N-Me)1Nal⁸]MGS5 showed the most promising targeting properties, with significantly increased accumulation of radioactivity in A431-CCK2R xenografts (48.1 ± 9.2% IA/g) and reduced accumulation of radioactivity in stomach (4.2 ± 0.5% IA/g). However, in comparison with DOTA-MGS5, a higher influence on the targeting properties was observed for the change of radiometal, resulting in a tumor uptake of 15.67 ± 2.21% IA/g for [⁶⁸Ga]Ga-DOTA-[(N-Me)1Nal⁸]MGS5 and 35.13 ± 6.32% IA/g for [¹⁷⁷Lu]Lu-DOTA-[(N-Me)1Nal⁸]MGS5. Full article

(This article belongs to the Special Issue Tumor-Targeting Radioligands for Molecular Imaging and Therapy)

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17 pages, 7264 KiB

Open AccessArticle

Optimized Therapeutic ¹⁷⁷Lu-Labeled PSMA-Targeted Ligands with Improved Pharmacokinetic Characteristics for Prostate Cancer

by Yitian Wu, Xiaojun Zhang, Xiaojiang Duan, Xing Yang, Feng Wang and Jinming Zhang

Pharmaceuticals 2022, 15(12), 1530; https://doi.org/10.3390/ph15121530 - 09 Dec 2022

Viewed by 1640

Abstract

Clinical trials have shown the significant efficacy of [¹⁷⁷Lu]Lu-PSMA-617 for treating prostate cancer. However, the pharmacokinetic characteristics and therapeutic performance of [¹⁷⁷Lu]Lu-PSMA-617 still need further improvement to meet clinical expectations. The aim of this study was to evaluate the feasibility and therapeutic potential of three novel ¹⁷⁷Lu-labeled ligands for the treatment of prostate cancer. The novel ligands were efficiently synthesized and radiolabeled with non-carrier added ¹⁷⁷Lu; the radiochemical purity of the final products was determined by Radio-HPLC. The specific cell-binding affinity to PSMA was evaluated in vitro using prostate cancer cell lines 22Rv1and PC-3. Blood pharmacokinetic analysis, biodistribution experiments, small animal SPCET imaging and treatment experiments were performed on normal and tumor-bearing mice. Among all the novel ligands developed in this study, [¹⁷⁷Lu]Lu-PSMA-Q showed the highest uptake in 22Rv1 cells, while there was almost no uptake in PC-3 cells. As the SPECT imaging tracer, [¹⁷⁷Lu]Lu-PSMA-Q is highly specific in delineating PSMA-positive tumors, with a shorter clearance half-life and higher tumor-to-background ratio than [¹⁷⁷Lu]Lu-PSMA-617. Biodistribution studies verified the SPECT imaging results. Furthermore, [¹⁷⁷Lu]Lu-PSMA-Q serves well as an effective therapeutic ligand to suppress tumor growth and improve the survival rate of tumor-bearing mice. All the results strongly demonstrate that [¹⁷⁷Lu]Lu-PSMA-Q is a PSMA-specific ligand with significant anti-tumor effect in preclinical models, and further clinical evaluation is worth conducting. Full article

(This article belongs to the Special Issue Tumor-Targeting Radioligands for Molecular Imaging and Therapy)

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12 pages, 2112 KiB

Open AccessArticle

Introduction of a SiFA Moiety into the D-Glutamate Chain of DOTA-PP-F11N Results in Radiohybrid-Based CCK-2R-Targeted Compounds with Improved Pharmacokinetics In Vivo

by Nadine Holzleitner, Thomas Günther, Roswitha Beck, Constantin Lapa and Hans-Jürgen Wester

Pharmaceuticals 2022, 15(12), 1467; https://doi.org/10.3390/ph15121467 - 25 Nov 2022

Cited by 6 | Viewed by 1710

Abstract

In order to enable ¹⁸F- and ¹⁷⁷Lu-labelling within the same molecule, we introduced a silicon-based fluoride acceptor (SiFA) into the hexa-D-glutamate chain of DOTA-PP-F11N. In addition, minigastrin analogues with a prolonged as well as γ-linked D-glutamate chain were synthesised and evaluated. CCK-2R affinity (IC₅₀, AR42J cells) and lipophilicity (logD_7.4) were determined. Biodistribution studies at 24 h post-injection (p.i.) and µSPECT/CT imaging at 1, 4 and 24 h p.i. were carried out in AR42J tumour-bearing CB17-SCID mice. CCK-2R affinity of (R)-DOTAGA-rhCCK-1 to 18 was enhanced with increasing distance between the SiFA building block and the binding motif. Lipophilicity of [¹⁷⁷Lu]Lu-(R)-DOTAGA-rhCCK-1 to 18 was higher compared to that of [¹⁷⁷Lu]Lu-DOTA-PP-F11N and [¹⁷⁷Lu]Lu-CP04. The respective α- and γ-linked rhCCK derivatives revealing the highest CCK-2R affinity were further evaluated in vivo. In comparison with [¹⁷⁷Lu]Lu-DOTA-PP-F11N, [¹⁷⁷Lu-]Lu-(R)-DOTAGA-rhCCK-9 and -16 exhibited three- to eight-fold increased activity levels in the tumour at 24 h p.i. However, activity levels in the kidneys were elevated as well. We could show that the introduction of a lipophilic SiFA moiety into the hydrophilic backbone of [¹⁷⁷Lu]Lu-DOTA-PP-F11N led to a decelerated blood clearance and thus improved tumour retention. However, elevated kidney retention has to be addressed in future studies. Full article

(This article belongs to the Special Issue Tumor-Targeting Radioligands for Molecular Imaging and Therapy)

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15 pages, 1675 KiB

Open AccessArticle

Synthesis and Evaluation of Two Long-Acting SSTR2 Antagonists for Radionuclide Therapy of Neuroendocrine Tumors

by Sofia Koustoulidou, Maryana Handula, Corrina de Ridder, Debra Stuurman, Savanne Beekman, Marion de Jong, Julie Nonnekens and Yann Seimbille

Pharmaceuticals 2022, 15(9), 1155; https://doi.org/10.3390/ph15091155 - 16 Sep 2022

Cited by 5 | Viewed by 2458

Abstract

Somatostatin receptor subtype 2 (SSTR2) has become an essential target for radionuclide therapy of neuroendocrine tumors (NETs). JR11 was introduced as a promising antagonist peptide to target SSTR2. However, due to its rapid blood clearance, a better pharmacokinetic profile is necessary for more effective treatment. Therefore, two JR11 analogs (8a and 8b), each carrying an albumin binding domain, were designed to prolong the blood residence time of JR11. Both compounds were labeled with lutetium-177 and evaluated via in vitro assays, followed by in vivo SPECT/CT imaging and ex vivo biodistribution studies. [¹⁷⁷Lu]Lu-8a and [¹⁷⁷Lu]Lu-8b were obtained with high radiochemical purity (>97%) and demonstrated excellent stability in PBS and mouse serum (>95%). [¹⁷⁷Lu]Lu-8a showed better affinity towards human albumin compared to [¹⁷⁷Lu]Lu-8b. Further, 8a and 8b exhibited binding affinities 30- and 48-fold lower, respectively, than that of the parent peptide JR11, along with high cell uptake and low internalization rate. SPECT/CT imaging verified high tumor accumulation for [¹⁷⁷Lu]Lu-8a and [¹⁷⁷Lu]Lu-JR11 at 4, 24, 48, and 72 h post-injection, but no tumor uptake was observed for [¹⁷⁷Lu]Lu-8b. Ex vivo biodistribution studies revealed high and increasing tumor uptake for [¹⁷⁷Lu]Lu-8a. However, its extended blood circulation led to an unfavorable biodistribution profile for radionuclide therapy. Full article

(This article belongs to the Special Issue Tumor-Targeting Radioligands for Molecular Imaging and Therapy)

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14 pages, 2134 KiB

Open AccessArticle

Optimization of the Pharmacokinetic Profile of [^99mTc]Tc-N₄-Bombesin Derivatives by Modification of the Pharmacophoric Gln-Trp Sequence

by Thomas Günther, Matthias Konrad, León Stopper, Jan-Philip Kunert, Sebastian Fischer, Roswitha Beck, Angela Casini and Hans-Jürgen Wester

Pharmaceuticals 2022, 15(9), 1133; https://doi.org/10.3390/ph15091133 - 10 Sep 2022

Cited by 3 | Viewed by 1815

Abstract

Current radiolabeled gastrin-releasing peptide receptor (GRPR) ligands usually suffer from high accumulation in GRPR-positive organs (pancreas, stomach), limiting tumor-to-background contrast in the abdomen. In novel N₄-bombesin derivatives this was addressed by substitutions at the Gln⁷-Trp⁸ site within the MJ9 peptide (H-Pip⁵-phe⁶-Gln⁷-Trp⁸-Ala⁹-Val¹⁰-Gly¹¹-His¹²-Sta¹³-Leu¹⁴-NH₂) either by homoserine (Hse⁷), β-(3-benzothienyl) alanine (Bta⁸) or α-methyl tryptophan (α-Me-Trp⁸), with the aim of optimizing pharmacokinetics. We prepared and characterized the peptide conjugates 6-carboxy-1,4,8,11-tetraazaundecane (N₄)-asp-MJ9, N₄-asp-[Bta⁸]MJ9, N₄-[Hse⁷]MJ9 and N₄-[α-Me-Trp⁸]MJ9, and evaluated these compounds in vitro (GRPR affinity via IC_50,inverse; internalization; lipophilicity via logD_7.4) and in vivo (biodistribution and μSPECT/CT studies at 1 h post injection (p.i.) in PC-3 tumor-bearing CB17-SCID mice). ^99mTc-labeling resulted in radiochemical yields (RCYs) > 95%. All ^99mTc-labeled MJ9 analogues showed comparable or higher GRPR affinity than the external reference [^99mTc]Tc-Demobesin 4. Receptor-bound fractions were noticeably higher than that of the reference. Despite a slightly enhanced lipophilicity, all novel MJ9 derivatives revealed improved in vivo pharmacokinetics compared to the reference. The Bta⁸-modified ligand revealed the most favorable tumor-to-abdomen contrast at 1 h p.i. Substitutions at the Gln⁷-Trp⁸ site within GRPR ligands hold great potential to modify pharmacokinetics for improved imaging. Full article

(This article belongs to the Special Issue Tumor-Targeting Radioligands for Molecular Imaging and Therapy)

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15 pages, 5652 KiB

Open AccessArticle

Comparison of the Anti-Tumour Activity of the Somatostatin Receptor (SST) Antagonist [¹⁷⁷Lu]Lu-Satoreotide Tetraxetan and the Agonist [¹⁷⁷Lu]Lu-DOTA-TATE in Mice Bearing AR42J SST₂-Positive Tumours

by Pascale Plas, Lorenzo Limana, Denis Carré, Amath Thiongane, Olivier Raguin, Rosalba Mansi, Florence Meyer-Losic and Stéphane Lezmi

Pharmaceuticals 2022, 15(9), 1085; https://doi.org/10.3390/ph15091085 - 30 Aug 2022

Cited by 1 | Viewed by 1958

Abstract

Limited experiments have compared the treatment effects of repetitive cycles of radiolabelled somatostatin (SST) analogues. In vitro and in vivo experiments were conducted in an AR42J cancer cell model, comparing the antagonist [¹⁷⁷Lu]Lu-satoreotide tetraxetan with the agonist [¹⁷⁷Lu]Lu-DOTA-TATE in terms of their binding properties, biodistribution, anti-tumour activity and toxicity. Histopathological and immunohistochemical examinations were performed at different timepoints. In the in vitro assays, [¹⁷⁷Lu]Lu-satoreotide tetraxetan recognised twice as many SST₂ binding sites as [¹⁷⁷Lu]Lu-DOTA-TATE. In mice treated once a week for four consecutive weeks, [¹⁷⁷Lu]Lu-satoreotide tetraxetan (15 MBq) revealed a significantly greater median time taken to reach a tumour volume of 850 mm³ (68 days) compared to [¹⁷⁷Lu]Lu-DOTA-TATE at 15 MBq (43 days) or 30 MBq (48 days). This was associated with a higher tumour uptake, enhanced DNA damage and no or mild effects on body weight, haematological toxicity, or renal toxicity with [¹⁷⁷Lu]Lu-satoreotide tetraxetan (15 MBq). At the end of the study, complete tumour senescence was noted in 20% of animals treated with [¹⁷⁷Lu]Lu-satoreotide tetraxetan, in 13% of those treated with [¹⁷⁷Lu]Lu-DOTA-TATE at 30 MBq, and in none of those treated with [¹⁷⁷Lu]Lu-DOTA-TATE at 15 MBq. In conclusion, repeated administrations of [¹⁷⁷Lu]Lu-satoreotide tetraxetan were able to potentiate peptide receptor radionuclide therapy with a higher tumour uptake, longer median survival, and enhanced DNA damage, with a favourable efficacy/safety profile compared to [¹⁷⁷Lu]Lu-DOTA-TATE. Full article

(This article belongs to the Special Issue Tumor-Targeting Radioligands for Molecular Imaging and Therapy)

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13 pages, 2090 KiB

Open AccessArticle

Optimization of Precursor Synthesis Conditions of (2S,4S)4–[¹⁸F]FPArg and Its Application in Glioma Imaging

by Yong Huang, Lu Zhang, Meng Wang, Chengze Li, Wei Zheng, Hualong Chen, Ying Liang and Zehui Wu

Pharmaceuticals 2022, 15(8), 946; https://doi.org/10.3390/ph15080946 - 29 Jul 2022

Cited by 2 | Viewed by 1545

Abstract

Although the tracer (2S,4S)4–[¹⁸F]FPArg is expected to provide a powerful imaging method for the diagnosis and treatment of clinical tumors, it has not been realized due to the low yield of chemical synthesis and radiolabeling. A simple synthetic method for the radiolabeled precursor of (2S,4S)4–[¹⁸F]FPArg in stable yield was obtained by adjusting the sequence of the synthetic steps. Furthermore, the biodistribution experiments confirmed that (2S,4S)4–[¹⁸F]FPArg could be cleared out quickly in wild type mouse. Cell uptake experiments and U87MG tumor mouse microPET–CT imaging experiments showed that the tumor had high uptake of (2S,4S)4–[¹⁸F]FPArg and the clearance was slow, but (2S,4S)4–[¹⁸F]FPArg was rapidly cleared in normal brain tissue. MicroPET–CT imaging of nude mice bearing orthotopic HS683–Luc showed that (2S,4S)4–[¹⁸F]FPArg can penetrate blood–brain barrier and image gliomas with a high contrast. Therefore, (2S,4S)4–[¹⁸F]FPArg is expected to be further applied in the diagnosis and efficacy evaluation of clinical glioma. Full article

(This article belongs to the Special Issue Tumor-Targeting Radioligands for Molecular Imaging and Therapy)

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13 pages, 2713 KiB

Open AccessArticle

[^99mTc]Tc-iFAP Radioligand for SPECT/CT Imaging of the Tumor Microenvironment: Kinetics, Radiation Dosimetry, and Imaging in Patients

by Luis Coria-Domínguez, Paola Vallejo-Armenta, Myrna Luna-Gutiérrez, Blanca Ocampo-García, Brenda Gibbens-Bandala, Francisco García-Pérez, Gerardo Ramírez-Nava, Clara Santos-Cuevas and Guillermina Ferro-Flores

Pharmaceuticals 2022, 15(5), 590; https://doi.org/10.3390/ph15050590 - 11 May 2022

Cited by 3 | Viewed by 2540

Abstract

Tumor microenvironment fibroblasts overexpress the fibroblast activation protein (FAP). We recently reported the preclinical evaluation of [^99mTc]Tc-iFAP as a new SPECT radioligand capable of detecting FAP. This research aimed to evaluate the kinetic and dosimetric profile of [^99mTc]Tc-iFAP in healthy volunteers, and to assess the radioligand uptake by different solid tumors in three cancer patients. [^99mTc]Tc-iFAP was obtained from lyophilized formulations prepared under GMP conditions with >98% radiochemical purity. Whole-body scans of six healthy subjects were obtained at 0.5, 2, 4, and 24 h after [^99mTc]Tc-iFAP (740 MBq) administration. A 2D-planar/3D-SPECT hybrid activity quantitation method was used to fit the biokinetic models of the source organs (volume of interest: VOI) as exponential functions (A(t)_VOI). The total nuclear transformations (N) that occurred in the source organs were calculated from the mathematical integration (0,∞) of A(t)_VOI. The OLINDA code was used to estimate the radiation doses. Three treatment-naive patients (breast, lung, and cervical cancer) with a prior [¹⁸F]FDG PET/CT scan underwent whole-body, chest, and abdominal SPECT/CT scanning after [^99mTc]Tc-iFAP (740 MBq) administration. Both imaging methods were compared visually and quantitatively. Oncological diagnoses were performed histopathologically. The results showed favorable [^99mTc]Tc-iFAP biodistribution and kinetics due to rapid blood activity removal (t_1/2α = 2.22 min and t_1/2β = 90 min) and mainly renal clearance. The mean radiation equivalent doses were 5.2 ± 0.8 mSv for the kidney and 1.7 ± 0.3 mSv for the liver after administration of 740 MBq. The effective dose was 2.3 ± 0.4 mSv/740 MBq. [^99mTc]Tc-iFAP demonstrated high and reliable uptake in the primary tumor lesions and lymph node metastases in patients with breast, cervical, and lung cancer, which correlated with that detected by [¹⁸F]FDG PET/CT. The tumor microenvironment molecular imaging from cancer patients obtained in this research validates the performance of additional clinical studies to determine the utility of [^99mTc]Tc-iFAP in the diagnosis and prognosis of different types of solid tumors. Full article

(This article belongs to the Special Issue Tumor-Targeting Radioligands for Molecular Imaging and Therapy)

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