Precision strikes: PSMA-targeted radionuclide therapy in prostate cancer - a narrative review.

Introduction: Radio-ligand targeted therapy is a new and promising concept of treatment Castration resistant prostate cancer (CRPC). Only a few radio-pharmaceutics were approved for usage in treating prostate cancer, among the multiple others tested. We aimed to review and summarize the literature on the therapeutic isotopes specific for PSMA. Methods: We performed a scoping literature review of PubMed from January 1996 to December 2022. Results: 98 publications were selected for inclusion in this review. The studies contained in publications allowed to summarize the data on pharmacokinetics, therapeutic effects, side effects and the medical use of 225Ac and 177Lu radionuclides. The review also presents new research directions for specific PSMA radionuclides. Conclusion: Radioligand targeted therapy is a new and promising concept where Lu-177-PSMA-617 have promising outcomes in treatment according to standard of care.

Radiation doses of employees of a Nuclear Medicine Department after implementation of more rigorous radiation protection methods.

The appropriate radiation protection measures applied in departments of nuclear medicine should lead to a reduction in doses received by the employees. During 1991-2007, at the Department of Nuclear Medicine of Pomeranian Medical University (Szczecin, Poland), nurses received on average two-times higher (4.6 mSv) annual doses to the whole body than those received by radiopharmacy technicians. The purpose of this work was to examine whether implementation of changes in the radiation protection protocol will considerably influence the reduction in whole-body doses received by the staff that are the most exposed. A reduction in nurses' exposure by ~63 % took place in 2008-11, whereas the exposure of radiopharmacy technicians grew by no more than 22 % in comparison with that in the period 1991-2007. Proper reorganisation of the work in departments of nuclear medicine can considerably affect dose reduction and bring about equal distribution of the exposure.

Prognostic value of myocardial perfusion scintigraphy for patients suspected of and diagnosed with coronary artery disease.

BACKGROUND: The prognostic value of myocardial perfusion scintigraphy (MPS) continues to attract interest and provoke discussions.This study was an attempt to investigate the methods. OBJECTIVE: Determination of the prognostic value of MPS for patients suspected of and diagnosed with coronary artery disease (CAD). MATERIAL AND METHODS: The study group included 215 patients, 134 males and 81 females, aged 21-66, mean age 48. Tc-99m-MIBI myocardial perfusion scintigraphy was performed and information concerning the diagnosis, aim of the examination, past coronary episodes, clinical condition, duration and type of complaints, concomitant diseases, test results, revascularisation procedures and pharmacological treatment was gathered. Further history of the patients was monitored throughout the observation period of 52 months on average. The patients were divided into the following two groups: Group I - suspected coronary artery disease: 124 patients aged 21-65,59 males and 65 females; Group II - diagnosed coronary artery disease: 91 patients aged 31-66, 75 males and 16 females diagnosed with CAD, including 39 s/p myocardial infarct, 31s/p infarct and revascularisation, 21 s/p revascularisation. The probability of CAD was calculated using the Diamond method for the patients suspected of CAD. The obtained results were examined in a statistical analysis. RESULTS: Normal MPS results were obtained for 94/124 patients suspected of CAD, 15/91 patients diagnosed with CAD,64/81 females and 45/134 males. In Group I, apart from pathological MPS results, reversible ischemia was determined in as many as 27/30 patients, and only 17/91 patients in Group II. No patients with normal MPS results suffered major cardiac events,only one of them underwent revascularisation. Major cardiac events occurred in the case of patients with pathological MPS results: Group I - 2 myocardial infarcts and 2 cardiac deaths,Group II - 3 infarcts and 10 cardiac deaths. Minor cardiac events, apart from one case, were also only observed in the case of patients with pathological MPS results: Group I - 10 revascularisations and one case of unstable CAD, Group II- 12 revascularisations and 7 cases of unstable CAD. Patients with normal MPS results and stenosis in coronary angioraphy suffered no cardiac events. Cardiac events occur mostly in the group with a medium and high risk of CAD and in the case of patients diagnosed with CAD. CONCLUSIONS: 1. Normal MPS results for patients suspected of or diagnosed with CAD: s/p infarct and/or CABG prognosticate a mild course of the disease, without or with a minimal number of cardiac events, also in a longer observation period.2. Pathological MPS results clearly imply a greater risk of cardiac events, and the number of events increases with the greater probability of CAD and with the patient's age. 3. Normal MPS results, even with significant stenosis in coronary angiography,prognosticate a low risk of cardiac events.

Dynamic renal scintigraphy with 99mTc-DTPA for the assessment of renal function after therapy of acute lymphoblastic leukemia in children.

INTRODUCTION: Acute lymphoblastic leukemia (ALL) and its treatment may lead to impairment of kidney function. The aim of the present study was to evaluate kidney function in children after treatment of ALL. We used our 99mTc-DTPA (diethylene triamine pentaacetic acid labeled with 99mTc) dynamic scintigraphy protocol. MATERIAL AND METHODS: The study group consisted of 48 ALL patients, aged 79-275 months, in complete remission (mean duration 51 months). Treatment was according to the guidelines of the Berlin Frankfurt Münster (BFM) BFM 86 and BFM 90 protocols in 36 (75%) and 12 (25%) children, respectively. Follow-up after treatment was up to 12 months in 10 (21%) children (group I), 12-60 months in 21 (44%) children (group II), and more than 60 months in 17 (35%) children (group III). 99mTc-DTPA dynamic renal scintigraphy was done in all patients. The glomerular filtration rate (GFR) was determined according to Gates and the diuretic test was done after 18 minutes of the examination. RESULTS: The glomerular filtration rate at the end of the 5-year follow-up was less than 80 mL/min/1.73 m2 (p < 0.002) in 3 (25%) children treated with the BFM 86 protocol. In the remaining 45 (94%) patients, GFR exceeded 80 mL/ min/1.73 m2. Normal renogram curves were obtained in 40 (83%) patients. Eight (17%) children had cumulative curves with normal clearance. This finding was interpreted as non-obstructive uropathy. There was no statistical correlation between outflow disorders seen during dynamic scintigraphy, type of chemotherapy protocol, and assignment to risks group. CONCLUSIONS: 1. There was no clinically significant kidney function impairment in children after treatment of ALL. 2. Dynamic renal scintigraphy can be a valuable and non-invasive method for the assessment of kidney function in patients with a risk factor in the form of previous potentially nephrotoxic antitumor treatment.

Patient-specific radiation dosimetry of 99mTc-HYNIC-Tyr3-octreotide in neuroendocrine tumors.

UNLABELLED: (99m)Tc-hydrazinonicotinamide-Tyr(3)-octreotide ((99m)Tc-HYNIC-TOC) is increasingly gaining acceptance as a new radiopharmaceutical for the diagnosis of pathologic lesions overexpressing somatostatin receptors. However, little information has been published about the radiation dosimetry of this agent. The aim of this study was to assess the biodistribution and radiation dosimetry of commercially available (99m)Tc-HYNIC-TOC. A dose calculation procedure designed to be feasible to implement in a busy clinical environment was used. METHODS: Twenty-eight patients were imaged for suspected neuroendocrine tumors using a series of whole-body planar, dynamic planar, and SPECT/CT studies, after injection with (99m)Tc-HYNIC-TOC. Patient-specific dosimetry was performed using the OLINDA/EXM software with time-integrated activity coefficients estimated from a hybrid planar/SPECT technique. A phantom experiment was performed to establish adaptive thresholds for determination of source region volumes and activities. RESULTS: Pathologic uptake, diagnosed as due to neuroendocrine tumors, was observed in 12 patients. Normal organs with significant uptake included the kidneys, liver, and spleen. The mean effective dose after (99m)Tc-HYNIC-TOC injection was 4.6 ± 1.1 mSv. Average normal-organ doses were 0.030 ± 0.012, 0.021 ± 0.007, and 0.012 ± 0.005 mGy/MBq for the spleen, kidneys, and liver, respectively. The interpatient kidney dose ranged from 0.011 to 0.039 mGy/MBq, whereas the range of tumor doses varied from 0.003 to 0.053 mGy/MBq. The ratio of tumor to kidney dose ranged from 0.13 to 2.9. The optimal thresholds for recovery of true activity in the phantom study were significantly lower than those used for volume determination. CONCLUSION: The patient-specific 3-dimensional dosimetry protocol used in this study is a clinically feasible technique that has been applied to demonstrate large dose variations in tumors and normal organs between patients imaged with (99m)Tc-HYNIC-TOC.

Static renal scintigraphy with 99mTc-DMSA for the assessment of renal damage after therapy for acute lymphoblastic leukemia in children.

INTRODUCTION: Acute lymphoblastic leukemia (ALL) and its treatment may adversely affect kidney function. The aim of the present study was to determine whether 99mTc-DMSA static renal scintigraphy can be used to disclose kidney damage at the end of therapy for ALL in children. MATERIAL AND METHODS: The study group consisted of 48 ALL patients aged 6.6-22.9 years, with a mean time of continuous complete remission of 51 months. Static renal scintigraphy with 99mTc-DMSA was performed in all patients. RESULTS: Minor scars in the renal cortex were diagnosed with scintigraphy in 6 (13%) patients. A significant correlation was found between renal scarring and a history of urinary tract infection. CONCLUSIONS: No clinically significant kidney damage was found after completion of treatment of ALL. Static renal scintigraphy may be a valuable noninvasive method for visualization of renal cortex pathology.

Effectiveness of strontium-89 palliative therapy in patients with painful bone metastases.

INTRODUCTION: Bone metastases are observed in 30-70% of patients with cancer. Painful bone metastases require regular control and treatment. Systemic palliative radiotherapy using beta-emitting radionuclides is an alternative method to analgesics and external beam radiotherapy. The aim of the study was to establish the efficacy and risk of side effects of radionuclide therapy in patients with bone metastases. MATERIAL AND METHODS: Strontium-89 (Sr-89) therapy was performed in 49 patients, 14 women and 35 men, aged 42-82 (mean 62) years with bone metastases confirmed by MDP-Tc99m whole body scan. The primary tumour was prostate cancer in 28 patients, breast cancer in 14, bladder cancer in 2, lung cancer in 2, gastric cancer in 2, and renal cancer in 1 patient. Intravenous injection of 150 MBq of Sr-89 was given and patients were observed for at least 3 months. Blood count, intensity of pain, drugs intake, life activity, and duration of effect were assigned 0-3 points. The overall response index was very good when the points totalled 10-12, good - 7-9, satisfactory - 4-6, poor - 2-3 and no response 0-1 points. Haemotoxicity was evaluated according to the Common Toxicity Criteria of the World Health Organisation (WHO). RESULTS: We found a very good response in 10 (20%) patients, good in 20 (41%), satisfactory in 8 (16%), poor in 2 (4%), and no response in 9 (19%) patients. Transient haemotoxicity of the Sr-89 therapy was observed in 39 (80%) patients. The mean decrease in platelets and leukocytes was 33-35%, but the haemoglobin concentration was reduced by only 15% in comparison to baseline values. The majority of patients did not require any treatment for haematologic side effects. Hospitalization was necessary in only 2 patients with grade 4 CTC WHO. CONCLUSION: Palliative radionuclide treatment of painful bone metastases with Strontium-89 in various primary tumours is in most cases an effective therapy with limited haemotoxicity.

Thyroid fine-needle aspiration biopsy: which lesions should be biopsied before 131I therapy?

INTRODUCTION: Suspicion of a neoplasm is one of the contraindications to radioiodine therapy in benign thyroid disease. The aim of this study was to present an optimal qualification scheme for fine-needle aspiration biopsy (FNAB) to rule out neoplastic lesions prior to radioiodine therapy. MATERIAL AND METHODS: 4207 patients with hyperthyroidism were referred for 131I therapy in 2000-2006. Prior to 131I therapy, all patients underwent thyroid function assessment, radioiodine uptake, scintigraphy, and ultrasound. Fine-needle aspiration biopsy with cytology was done in 578 (13.7%) patients. Therapeutic radioiodine was administered to 3564 (84.7%) patients. RESULTS: Malignancy was confirmed or suspected in 12 female patients (0.28% of all patients and 2.07% of patients who underwent FNAB). Prior to the study, cytology was done in only one patient. The diameter of the lesions was 6-28 mm. Cytology confirmed papillary carcinoma in 4 patients, follicular tumour in 6, and Hürthle's cell tumour in 1. There were indications for histopathology in one patient due to the presence of atypical cells. The primary diagnosis was toxic nodular goitre in 8 patients and Graves' disease in 4 patients. One of the patients with follicular tumour was referred for radioiodine therapy due to intolerance to thyrostatic drugs, elderly age, and comorbidities. CONCLUSIONS: 1. Thyroid scintigraphy prior to therapy is important for the choice of the site of FNAB. 2. Thyroid lesions in patients with nodular Graves' disease must be carefully investigated to exclude malignancy. 3. Preselection of patients for treatment of benign thyroid disease should be followed by cytology of the lesions at the Department of Nuclear Medicine.

Response of malignant breast tumours to neoadjuvant chemotherapy evaluated with Tc-99m MIBI.

INTRODUCTION: The aim of this study was to assess the efficacy of Tc-99m sestamibi scintimammography in the prediction and evaluation of tumour response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. MATERIALS AND METHODS: The subjects consisted of 14 female patients with unilateral locally advanced breast cancer eligible for anthracycline-based neoadjuvant chemotherapy followed by surgery. The patients underwent mastectomies with pathologic evaluation of the residual tumour size. The early and delayed static imaging were undertaken in all subjects at 10 and 120 minutes after intravenous injection with 720-1080 MBq of Tc-99m MIBI. Patients lay prone on the scintimammographic pad (provided by the IAEA). The acquisition included three positions: both lateral prone and anterior supine. Early, delayed tumour to background ratios (TBR) and washout rate (WOR) were calculated. Three sets of scintimammography images were obtained: baseline study (BL), the first follow-up study (FF) after two cycles of chemotherapy and the second follow-up (SF) scan on completion of chemotherapy and prior to surgery. Clinical response was evaluated following WHO criteria and classified as complete response (CR), partial response (PR), stable disease (StD) and progressive disease (PD). All patients underwent BS, seven of them FF and eight completed the study with SF. RESULTS: The only statistically significant differences in Student's t-test for matched pairs were found between mean values of TBR10 and TBR120 in BL and FF study however in the SF study it was not significant. Other differences between the mean values of TBR10, TBR120 and WOR in BL/FF, BL/SF and FF/SF studies were not statistically significant. CONCLUSION: The results obtained are encouraging, but further investigations are needed.

The application of SPECT/CT scintigraphy with MIBI-Tc99(m) in the diagnosis of thyroid nodules - a preliminary report.

INTRODUCTION: Thyroid cancer diagnosis is based mainly on fine needle aspiration biopsy (FNAB) performed under ultrasonography guidance. Questions arise in cases of an inconclusive FNAB result - when there is no clear evidential data to support the existence of a malignant lesion or when there are any other reasons which make the decision process difficult, such as the patient's age or coexisting diseases. To clarify this issue the patient should be encouraged to undergo surgery treatment or to be followed up. Thyroid scintigraphy with an oncophilic tracer such as MIBI-Tc99(m) may be helpful. MATERIAL AND METHODS: The study comprised a group of 12 patients, aged 54-75 (av. 63.5) years, who, in 2009, underwent planar and SPECT/CT thyroid scintigraphy with MIBI-Tc99(m) using washout method. The tumour/background ratio in early and delayed images was calculated and the wash-out ratio was estimated. Patients with increased focal lesion uptake were operated on and the lesions were histopathologically verified. RESULTS: Abnormal scintigraphy results were obtained in 8 patients (10 lesions) and normal results in 4 patients (5 lesions). Out of 15 studies, in 13 cases the washout from the lesion was observed within 2 hours. It was noticed that the images obtained with SPECT/CT washout method were clearer and easier to read in comparison to planar studies. Three patients with an abnormal results underwent surgery and had benign histopathology results after the operation, in 3 patients the observation is being confirmed without any increase in malignancy suspicions, and 2 were lost for observation. CONCLUSIONS: Our preliminary results do support the use of MIBI-Tc99m in the evaluation of indeterminate thyroid nodules. To validate the hypothesis that MIBI-Tc99(m) may be used to exclude malignancy in lesions indeterminate by FNAB we propose to use SPECT-CT derived images and standardized evaluation criteria.

Optimization of low-dose CT protocol in pediatric nuclear medicine imaging.

UNLABELLED: This study was performed to find the optimal low-dose CT protocol for children being imaged on SPECT/CT scanners not equipped with automatic dose control. For SPECT/CT systems with manually adjustable x-ray tube voltage (kV) and anode current (mA), an optimized protocol makes it possible to minimize the dose to patients. METHODS: Using the 4-slice low-dose CT component of a commercially available SPECT/CT scanner, we compared the signals reaching the CT detector after radiation passes through objects of different sizes. First, the exit dose rates were measured for combinations of available voltages and currents. Next, imaging parameters were selected on the basis of acceptable levels of exit dose rates, cylindric phantoms of different diameters approximating children of different sizes were scanned using these parameters, and the quality of the CT images was evaluated. Finally, weighted CT dose indexes for abdomen and head CT dose phantoms simulating, respectively, adult and pediatric patients were measured using exactly the same techniques to estimate and compare doses to these 2 groups of patients. RESULTS: For children with torsos smaller than 150 mm, imaging can be performed using the lowest available voltage and current (120 kV and 1 mA, respectively). For children with torsos less than 250 mm, 140 kV and 1.5 mA can be used. For patients with torsos greater than 250 and less than 300 mm, 140 kV and 2 mA can be used. Regarding the signal-to-noise ratio, all these parameters give an excellent signal and fully acceptable noise levels. CONCLUSION: For the SPECT/CT system studied, even the lowest available voltage and current used for scanning pediatric patients did not cause signal-to-noise degradation, and the use of these settings substantially lowered the dose to the patients.

[Diagnostic value of 99mTc-MIBI myocardial perfusion SPECT in women with suspected coronary artery disease]. / Wartosc diagnostyczna scyntygrafii perfuzyjnej serca SPECT z uzyciem 99mTc-MIBI u kobiet z podejrzeniem choroby wiencowej.

INTRODUCTION: Coronary artery disease is the leading cause of mortality in the general population. Women constitute a special group of patients due to the fact that clinical presentation in women is less characteristic and diagnostic tests are more difficult to interpret. The representation by men in clinical trials grossly exceeds that by women and the number of investigations conducted selectively in women remains too small. The aim of this study was to evaluate the diagnostic usefulness of myocardial perfusion scintigraphy (SPS) with 99mTc-MIBI in women with suspected coronary artery disease, particularly in those with nondiagnostic or positive stress electrocardiography (SEKG), to assess the prognostic value of SPS during a 4-year follow-up targeting serious cardiac events, and to compare the results of SPS with SEKG and coronary angiography. MATERIAL AND METHODS: We enrolled 230 women with a moderate probability of coronary artery disease estimated on the basis of clinical scales and SEKG. A 2-day stress/ rest SPS was done in all patients. The clinical course was determined in 157 patients. It was found that the 1-year risk of a serious cardiac event in women with an abnormal SPS was 7.9%, as opposed to 1.7% in women with a normal SPS. RESULT: The results confirmed the high prognostic value of SPS in predicting serious cardiac events (p = 0.01). There was no statistically significant correlation between ambulant SEKG and SPS (p = 0.06). Similarly, the results of SEKG did not correlate with serious cardiac events (p = 0.35). The prognostic value of SPS found by us was high, and moreover, SPS turned out to be superior over SEKG in our study group. CONCLUSION: Myocardial perfusion scintigraphy emerged as a good diagnostic tool in women with suspected coronary artery disease. Myocardial perfusion scintigraphy is helpful in verifying the need for further diagnostic tests in women, especially with positive or nondiagnostic SEKG.

Does Hynes-Anderson pyeloplasty improve renal function?

INTRODUCTION: With the advent of renoscintigraphy, improvement in renal function after Hynes-Anderson pyeloplasty became and continues to be an object of interest. We performed a retrospective analysis in a group of our patients with the hope of resolving some issues. MATERIAL: Medical files with complete renoscintigraphic data of 51 patients with symptomatic hydronephrosis who underwent Hynes-Anderson pyeloplasty between 1996 and 2002 were analyzed. Two study groups were formed: patients operated before the age of 12 months (n = 18, mean age 4 months), and patients operated after the age of 12 months (n = 33, mean age 8 years). METHODS: Renoscintigraphic imaging was performed using DTPA according to EANM guidelines. The following parameters were analyzed: differential renal function--DRF (%), glomerular filtration rate--GFR (mL/min), and type ofrenoscintigraphy (1--non-obstructive, 2--equivocal, 3--obstructive). Renoscintigraphy was done preoperatively, 3 and 12 months after surgery, and at the end of the follow-up. The level of significance was taken as p < or = 0.05. RESULTS: Preoperative DRF values in both groups (46 +/- 8 and 44 +/- 9) revealed no significant differences; GFR values (18 +/- 14 and 36 +/- 17) revealed significant differences (p < 0.001) between the groups. 55% of patients in each group had obstructive renoscintigraphy (2.3 +/- 0.9 and 2.2 +/- 0.9, respectively). Preoperative and consecutive postoperative DRF values did not reveal any significant differences. A progressive increase in GFR was noted in infants: the change was insignificant after three months from surgery, becoming significant after 12 months (p = 0.007), and reaching 45.6 +/- 7.1 (p = 0.02) at the end of follow-up. No significant differences were found in older children. Significant improvement in drainage noted three months after surgery in both groups (1.6 +/- 0.9; p = 0.008 and 1.4 +/- 0.8; p = 0.001) did not reveal any further change. CONCLUSIONS: 1. Hynes-Anderson pyeloplasty had no effect on DRF values in most patients regardless of age and initial renal function. 2. The increase in GFR in children operated before the first year of life seems attributable to the growth potential of the kidney, although surgery could have created conditions for full emergence of this potential. 3. Obstructive renoscintigraphy is not an unequivocal proof for clinically significant urine outflow obstruction; this can be demonstrated by clinical symptoms.

Strontium-89 in palliative treatement of painfull bone metastases.

Background. Bone metastases are observed in 30-70% of patients with cancer. Pain is most frequent symptom that requires regular control and treatment. Systemic palliative radionuclide therapy using beta-emitters is alternative method for analgetic drugs and external beam radiotherapy. The aim of the study was to establish efficacy and risk of side effects of radionuclide treatment in patients with painful osseous metastases.
Material and methods. Sr-89 therapy was performed in 33 patients 13 women and 13 men aged 42 to 79 years (mean 61) with cancer and bone metastases confirmed in MDP-Tc99m whole body scan. Prostate cancer was primary tumour in 18 patients, breast cancer in 12, urinary bladder cancer in 2 and renal cancer in 1 patient.
After intravenous administration of 150 MBq of strontium-89 chloride patients were observed during
3 months and more. Changes in blood counts, intensity of pain, drugs intake, life activity and duration of pain relief was evaluated from 0 to 3 points. Overall Response Index was very good if total points amounted 10-12, good - 7-9, satisfying - 4-6, poor - 2-3 and no response 0-1 points. Myelosuppression was evaluated according to Common Toxicity Criteria by WHO.
Results. Very good response in 6 patients (18%), good in 15 (46%), satisfying in 6 (18%), poor in 2 (6%) and no response in 4 (12%) patients. Transient haemotoxicity post Sr-89 therapy was observed in 16 patients (48%), in 11 patients it was grade I CTC, in 1 grade II CTC, in 3 grade 3 CTC and in one man grade IV which required treatment. Duration of life after therapy was between 21 to 138 weeks (mean 58 weeks). Therapy was repeated in 16 (48%) patients after more than 3 months. Third dose was injected in 2 patients (6%).
Conclusions. Palliative strontium-89 treatment of painful osseous metastases is effective therapy with very mild haemotoxicity.