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1.  131I-Tositumomab Myeloablative Radioimmunotherapy for Non-Hodgkin Lymphoma: Radiation Dose to Testes 
Nuclear medicine communications  2012;33(12):1225-1231.
To investigate radiation dose to testes delivered by radiolabeled anti-CD20 antibody and its effects on male sex hormone levels.
Testicular uptake and retention of 131I tositumomab were measured and testicular absorbed doses were calculated for 67 male patients (54 ± 11 years old) with non-Hodgkin lymphoma who underwent myeloablative radioimmunotherapy (RIT) using 131I-tositumomab. Time-activity curves for the major organs, testes, and whole body were generated from planar imaging. In a subset of patients, male sex hormones were measured before and one year after the therapy.
Absorbed dose to testes showed considerable variability (range = 4.4 to 70.2 Gy). Pre-therapy levels of total testosterone were below the lower limit of the reference range, and post-therapy evaluation demonstrated further reduction (4.6 ± 1.8 nmol/L (pre-RIT) vs. 3.8 ± 2.9 nmol/L (post-RIT), p < 0.05). Patients receiving higher radiation doses to the testes (≥ 25 Gy) showed a greater reduction (4.7 ± 1.6 nmol/L (pre RIT) vs. 3.3 ± 2.7 nmol/L (post-RIT), p < 0.05) than did patients receiving lower doses (< 25 Gy), who showed no significant change in total testosterone levels.
The testicular radiation absorbed dose varied highly among individual patients. Patients receiving higher doses to testes were more likely to show post-RIT suppression of testosterone levels.
PMCID: PMC3703155  PMID: 22955187
131I-tositumomab; follicular lymphoma; radioimmunotherapy; radiation dosimetry; male sex hormones
2.  PR-104 a bioreductive pre-prodrug combined with gemcitabine or docetaxel in a phase Ib study of patients with advanced solid tumours 
BMC Cancer  2012;12:496.
The purpose of this phase Ib clinical trial was to determine the maximum tolerated dose (MTD) of PR-104 a bioreductive pre-prodrug given in combination with gemcitabine or docetaxel in patients with advanced solid tumours.
PR-104 was administered as a one-hour intravenous infusion combined with docetaxel 60 to 75 mg/m2 on day one given with or without granulocyte colony stimulating factor (G-CSF) on day two or administrated with gemcitabine 800 mg/m2 on days one and eight, of a 21-day treatment cycle. Patients were assigned to one of ten PR-104 dose-levels ranging from 140 to 1100 mg/m2 and to one of four combination groups. Pharmacokinetic studies were scheduled for cycle one day one and 18F fluoromisonidazole (FMISO) positron emission tomography hypoxia imaging at baseline and after two treatment cycles.
Forty two patients (23 females and 19 males) were enrolled with ages ranging from 27 to 85 years and a wide range of advanced solid tumours. The MTD of PR-104 was 140 mg/m2 when combined with gemcitabine, 200 mg/m2 when combined with docetaxel 60 mg/m2, 770 mg/m2 when combined with docetaxel 60 mg/m2 plus G-CSF and ≥770 mg/m2 when combined with docetaxel 75 mg/m2 plus G-CSF. Dose-limiting toxicity (DLT) across all four combination settings included thrombocytopenia, neutropenic fever and fatigue. Other common grade three or four toxicities included neutropenia, anaemia and leukopenia. Four patients had partial tumour response. Eleven of 17 patients undergoing FMISO scans showed tumour hypoxia at baseline. Plasma pharmacokinetics of PR-104, its metabolites (alcohol PR-104A, glucuronide PR-104G, hydroxylamine PR-104H, amine PR-104M and semi-mustard PR-104S1), docetaxel and gemcitabine were similar to that of their single agents.
Combination of PR-104 with docetaxel or gemcitabine caused dose-limiting and severe myelotoxicity, but prophylactic G-CSF allowed PR-104 dose escalation with docetaxel. Dose-limiting thrombocytopenia prohibited further evaluation of the PR104-gemcitabine combination. A recommended dose was identified for phase II trials of PR-104 of 770 mg/m2 combined with docetaxel 60 to 75 mg/m2 both given on day one of a 21-day treatment cycle supported by prophylactic G-CSF (NCT00459836).
PMCID: PMC3495895  PMID: 23098625
3.  Bilateral massive pulmonary thromboembolism in a young patient treated with supportive measures and an inferior vena cava filter with excellent outcome 
Acute pulmonary embolism (PE) is a common and often fatal disease with a mortality rate of more than 30% in untreated patients. There is a twofold increase in mortality in patients with massive PEs who do not receive treatment. Recurrent embolism is the most common cause of death. A 48-year-old woman presented to Tan Tock Seng Hospital, Singapore, on December 16, 2009, with a massive pulmonary thromboembolism. She was admitted to the intensive care unit and treated with supportive measures, ventilatory support, antibiotics and ionotropes. The patient was diagnosed with urosepsis with septicemic shock, disseminated intravascular coagulation, acute renal failure, high anion gap metabolic acidosis, iron-deficiency anemia secondary to menorrhagia, and a uterine mass with high cancer antigen 125, although malignancy was ruled out. Anticoagulation or thrombolysis could not be provided in view of coagulopathy. The patient subsequently underwent inferior vena cava filter insertion on December 31, 2009. The patient showed clinical improvement over the next two weeks with antibiotics and supportive measures. If there is a contraindication to anticoagulation or thrombolysis, massive pulmonary thromboembolism should be treated aggressively with supportive measures. Inferior vena cava filter insertion should be instituted early to prevent recurrent PE, which can be fatal. It may take weeks before the patient displays clinical improvement.
PMCID: PMC3014592  PMID: 22477620
High CA 125; Inferior vena cava filter; Massive pulmonary embolism; No anticoagulation; No thrombolysis
4.  Challenges in Clinical Studies with Multiple Imaging Probes 
Nuclear medicine and biology  2007;34(7):879-885.
This essay addresses two related issues: (1) When a new imaging agent is proposed, how does the imager integrate it with other biomarkers, either sampled or imaged? (2) When we have multiple imaging agents, is the information additive or duplicative and how is this objectively determined? Molecular biology is leading to new treatment options with reduced normal tissue toxicity, and imaging should have a role in objectively evaluating new treatments. There are two roles for molecular characterization of disease. Molecular imaging measurements before therapy help predict the aggressiveness of disease and identify therapeutic targets, and therefore help choose the optimal therapy for an individual. Measurements of specific biochemical processes made during or after therapy should be sensitive measures of tumor response. The rules of evidence are not fully developed for the prognostic role of imaging biomarkers but the potential of molecular imaging provides compelling motivation to push forward with convincing validation studies. New imaging procedures need to be characterized for their effectiveness under realistic clinical conditions to improve the management of patients and achieve a better outcome. The purpose of this essay is to promote a critical discussion within the molecular imaging community because our future value to the overall biomedical community will be in supporting better treatment outcomes more than in detection.
PMCID: PMC2099630  PMID: 17921038

Results 1-4 (4)